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Abstract Acquired resistance to PARP inhibitors (PARPi) remains a treatment challenge for BRCA1/2-mutant breast cancer that drastically shortens patient survival. Although several resistance mechanisms have been identified, none have been successfully targeted in the clinic. Using new PARPi-resistance models of Brca1- and Bard1-mutant breast cancer generated in-vivo, we identified FLT1 (VEGFR1) as a driver of resistance. Unlike the known role of VEGF signaling in angiogenesis, we demonstrate a novel, non-canonical role for FLT1 signaling that protects cancer cells from PARPi in-vivo through a combination of cell-intrinsic and cell-extrinsic pathways. We demonstrate that FLT1 blockade suppresses AKT activation, increases tumor infiltration of CD8+ T cells, and causes dramatic regression of PARPi-resistant breast tumors in a T-cell-dependent manner. Moreover, PARPi-resistant tumor cells can be readily re-sensitized to PARPi by targeting Flt1 either genetically (Flt1-suppression) or pharmacologically (axitinib). Importantly, a retrospective series of breast cancer patients treated with PARPi demonstrated shorter progression-free survival in cases with FLT1 activation at pre-treatment. Our study therefore identifies FLT1 as a potential therapeutic target in PARPi-resistant, BRCA1/2-mutant breast cancer.

BackgroundThe misuse and overuse of antibiotics accelerate the development of antimicrobial resistance (AMR). Serious games, any form of games that serve a greater purpose other than entertainment, could augment public education above ongoing health promotion efforts. Hence, we developed an evidence-based educational serious game app—SteWARdS Antibiotic Defence—to educate players on good antibiotic use practices and AMR through a game quest comprising 3 minigames and interaction with the nonplayer characters. ObjectiveWe aimed to evaluate the effectiveness of the SteWARdS Antibiotic Defence app in improving the knowledge of, attitude toward, and perceptions (KAP) of appropriate antibiotic use and AMR among the public in Singapore. MethodsWe conducted a 2-arm parallel randomized controlled trial, recruiting visitors aged 18-65 years from 2 polyclinics in Singapore. Intervention group participants had to download the SteWARdS Antibiotic Defence app (available only in English and on the Android platform) on their smartphones and complete the quest in the app. Participants took half a day to 2 weeks to complete the quest. The control group received no intervention. Knowledge questions on antibiotic use and AMR (11 binary questions) were self-administered at baseline, immediately after the intervention, and 6-10 weeks post intervention, while attitudes and perception questions (14 three-point Likert-scale questions) were self-administered at baseline and 6-10 weeks post intervention. We also collected participants’ feedback on app usage. ResultsParticipants (n=348; intervention: n=142, control: n=206) had a mean age of 36.9 years. Intervention group participants showed a statistically significant improvement in mean knowledge score (effect size: 0.58 [95% CI 0.28-0.87]) compared with controls after accounting for age, educational level, and exposure to advertisements on antibiotics and AMR. Intervention participants also showed a statistically significant improvement in mean attitude-perception scores (effect size: 0.98 (95% CI 0.44-1.52)) after adjusting for marital status and race. A majority of participants agreed that the “SteWARdS Antibiotic Defence” app improved their awareness on antibiotic use (135/142, 95.1%) and AMR (136/142, 95.8%). About 73.9% (105/142) of the participants agreed that the app is easy to use, 70.4% (100/142) agreed that the app was enjoyable, and 85.2% (121/142) would recommend the app to others. ConclusionsOur educational serious game app improves participants’ KAP on appropriate antibiotic use and AMR. Public education apps should be engaging, educational, easy to use, and have an attractive user interface. Future research should assess the effectiveness of interventions in facilitating long-term knowledge retention and long-lasting behavioral change. Trial RegistrationClinicalTrials.gov NCT05445414; https://clinicaltrials.gov/ct2/show/NCT05445414 International Registered Report Identifier (IRRID)RR2-10.2196/45833

BackgroundShared decision-making (SDM) on antibiotic therapy may improve antibiotic use in tertiary hospitals, but hospitalised patients are apprehensive about being involved in it. Understanding the facilitators and barriers to SDM can inform the design and implementation of interventions to empower these patients to engage in SDM on their antibiotic therapies.MethodsWe conducted qualitative interviews with 23 adult patients purposively sampled with maximum variation from the three largest tertiary-care hospitals in Singapore (April 2019─October 2020). Thematic analysis was conducted using the Theoretical Domains Framework and Capability, Opportunity, Motivation, Behaviour (COM-B) model to identify areas for intervention.ResultsHospitalised patients lacked comprehensive knowledge of their antibiotic therapies and the majority did not have the skills to actively query their doctors about them. There was a lack of opportunities to meet and interact with doctors, and patients were less motivated to engage in SDM if they had a self-perceived paternalistic relationship with doctors, trusted their doctors to provide the best treatment, and had self-perceived poor knowledge to engage in SDM. To empower these patients, they should first be educated with antibiotic knowledge. Highlighting potential side effects of antibiotics could motivate them to ask questions about their antibiotic therapies. Environment restructuring, as facilitated by nurses and visual cues to nudge conversations, could create opportunities for interactions and motivating patients into SDM on their antibiotic therapies.ConclusionEducation and environmental restructuring should be explored to empower hospitalised patients to engage in SDM on their antibiotic therapies.

ObjectivesThe increased utilization of Artificial intelligence (AI) in healthcare changes practice and introduces ethical implications for AI adoption in medicine. We assess medical doctors’ ethical stance in situations that arise in adopting an AI-enabled Clinical Decision Support System (AI-CDSS) for antibiotic prescribing decision support in a healthcare institution in Singapore.MethodsWe conducted in-depth interviews with 30 doctors of varying medical specialties and designations between October 2022 and January 2023. Our interview guide was anchored on the four pillars of medical ethics. We used clinical vignettes with the following hypothetical scenarios: (1) Using an antibiotic AI-enabled CDSS’s recommendations for a tourist, (2) Uncertainty about the AI-CDSS’s recommendation of a narrow-spectrum antibiotic vs. concerns about antimicrobial resistance, (3) Patient refusing the “best treatment” recommended by the AI-CDSS, (4) Data breach.ResultsMore than half of the participants only realized that the AI-enabled CDSS could have misrepresented non-local populations after being probed to think about the AI-CDSS’s data source. Regarding prescribing a broad- or narrow-spectrum antibiotic, most participants preferred to exercise their clinical judgment over the AI-enabled CDSS’s recommendations in their patients’ best interest. Two-thirds of participants prioritized beneficence over patient autonomy by convincing patients who refused the best practice treatment to accept it. Many were unaware of the implications of data breaches.ConclusionThe current position on the legal liability concerning the use of AI-enabled CDSS is unclear in relation to doctors, hospitals and CDSS providers. Having a comprehensive ethical legal and regulatory framework, perceived organizational support, and adequate knowledge of AI and ethics are essential for successfully implementing AI in healthcare.

ABSTRACT: Objectives: Artificial intelligence (AI)-driven clinical decision support systems (CDSSs) can augment antibiotic decision-making capabilities, but physicians’ hesitancy in adopting them may undermine their utility. We conducted a cross-country comparison of physician perceptions on the barriers and facilitators in accepting an AI-enabled CDSS for antibiotic prescribing. Methods: We conducted in-depth interviews with physicians from the National Centre for Infectious Diseases (NCID), Singapore, and Christian Medical College Vellore (CMCV), India, between April and December 2022. Our semi-structured in-depth interview guides were anchored on Venkatesh's UTAUT model. We used clinical vignettes to illustrate the application of AI in clinical decision support for antibiotic prescribing and explore medico-legal concerns. Results: Most NCID physicians felt that an AI-enabled CDSS could facilitate antibiotic prescribing, while most CMCV physicians were sceptical about the tool's utility. The hesitancy in adopting an AI-enabled CDSS stems from concerns about the lack of validated and successful examples, fear of losing autonomy and clinical skills, difficulty of use, and impediment in work efficiency. Physicians from both sites felt that a user-friendly interface, integration with workflow, transparency of output, a guiding medico-legal framework, and training and technical support would improve the uptake of an AI-enabled CDSS. Conclusion: In conclusion, the acceptance of AI-enabled CDSSs depends on the physician's confidence with the tool's recommendations, perceived ease of use, familiarity with AI, the organisation's digital culture and support, and the presence of medico-legal governance of AI. Progressive implementation and continuous feedback are essential to allay scepticism around the utility of AI-enabled CDSSs.

BackgroundAntimicrobial stewardship programs attempting to optimize antibiotic therapy and clinical outcomes mainly focus on inpatient and outpatient settings. The lack of antimicrobial stewardship program studies in the emergency department (ED) represents a gap in tackling the problem of antimicrobial resistance as EDs treat a substantial number of upper respiratory tract infection cases throughout the year. ObjectiveWe intend to implement two evidence-based interventions: (1) patient education and (2) providing physician feedback on their prescribing rates. We will incorporate evidence from a literature review and contextualizing the interventions based on findings from a local qualitative study. MethodsOur study uses a quasi-experimental design to evaluate the effects of interventions over time in the EDs of 4 public hospitals in Singapore. We will include an initial control period of 18 months. In the next 6 months, we will randomize 2 EDs to receive 1 intervention (ie, patient education) and the other 2 EDs to receive the alternative intervention (ie, physician feedback). All EDs will receive the second intervention in the subsequent 6 months on top of the ongoing intervention. Data will be collected for another 6 months to assess the persistence of the intervention effects. The information leaflets will be handed to patients at the EDs before they consult with the physician, while feedback to individual physicians by senior doctors is in the form of electronic text messages. The feedback will contain the physicians’ antibiotic prescribing rate compared with the departments’ overall antibiotic prescribing rate and a bite-size message on good antibiotic prescribing practices. ResultsWe will analyze the data using segmented regression with difference-in-difference estimation to account for concurrent cluster comparisons. ConclusionsOur proposed study assesses the effectiveness of evidence-based, context-specific interventions to optimize antibiotic prescribing in EDs. These interventions are aligned with Singapore’s national effort to tackle antimicrobial resistance and can be scaled up if successful. Trial RegistrationClinicalTrials.gov NCT05451863; https://clinicaltrials.gov/study/NCT05451836 International Registered Report Identifier (IRRID)DERR1-10.2196/50417

ABSTRACT: Objectives: Pre-COVID-19 pandemic, patients who attended the emergency department (ED) for upper respiratory tract infection (URTI) were more likely to receive antibiotics if they expected them. These expectations could have changed with the change in health-seeking behaviour during the pandemic. We assessed the factors associated with antibiotics expectation and receipt for uncomplicated URTI patients in four Singapore EDs during the COVID-19 pandemic. Methods: We conducted a cross-sectional study on adult patients with URTI from March 2021 to March 2022 in four Singapore EDs and assessed the determinants of antibiotics expectation and receipt using multivariable logistic regression models. We also assessed the reasons patients expect antibiotics during their ED visit. Results: Among 681 patients, 31.0% expected antibiotics while 8.7% received antibiotics during their ED visit. Factors (adjusted odds ratio [95% confidence interval]) that significantly influenced expectation for antibiotics include: 1) prior consultation for current illness with (6.56 [3.30–13.11]) or without (1.50 [1.01–2.23]) antibiotics prescribed; 2) anticipation for COVID-19 test (1.56 [1.01–2.41]); and 3) poor (2.16 [1.26–3.68]) to moderate (2.26 [1.33–3.84]) knowledge on antibiotics use and resistance. Patients expecting antibiotics were 10.6 times (10.64 [5.34–21.17]) more likely to receive antibiotics. Those with tertiary education were twice (2.20 [1.09–4.43]) as likely to receive antibiotics. Conclusion: In conclusion, patients with URTI who expected antibiotics to be prescribed remained more likely to receive it during the COVID-19 pandemic. This highlights the need for more public education on the non-necessity for antibiotics for URTI and COVID-19 to address the problem of antibiotic resistance.

BackgroundThe uncertainties surrounding the COVID-19 pandemic led to a surge in non-urgent emergency department (ED) attendance among people presenting with upper respiratory tract infection (URTI) symptoms. These non-urgent visits, often manageable in primary care, exacerbated ED overcrowding, which could compromise the quality of ED services. Understanding patients' expectations and the reasons for these ED visits is imperative to mitigate the problem of ED overcrowding. Hence, we assessed the factors influencing patients' expectations for diagnostic tests during their ED visits for uncomplicated URTI during different phases of the pandemic.MethodsWe conducted a cross-sectional study on adults with URTI symptoms seeking care at four public EDs in Singapore between March 2021 and March 2022. We segmented the study period into three COVID-19 pandemic phases—containment, transition, and mitigation. The outcome variables are whether patients expected (1) a COVID-19-specific diagnostic test, (2) a non-COVID-19-specific diagnostic test, (3) both COVID-19-specific and non-COVID-19-specific diagnostic tests, or (4) no diagnostic test. We built a multinomial regression model with backward stepwise selection and classified the findings according to Andersen's healthcare utilization model.ResultsThe mean age of participants was 34.5 (12.7) years. Factors (adjusted odds ratio [95% confidence interval]) influencing expectations for a COVID-19-specific diagnostic test in the ED include younger age {21–40 years: (2.98 [1.04–8.55])}, no prior clinical consultation (2.10 [1.13–3.89]), adherence to employer's health policy (3.70 [1.79–7.67]), perceived non-severity of illness (2.50 [1.39–4.55]), being worried about contracting COVID-19 (2.29 [1.11–4.69]), and during the transition phase of the pandemic (2.29 [1.15–4.56]). Being non-employed influenced the expectation for non-COVID-19-specific diagnostic tests (3.83 [1.26–11.66]). Factors influencing expectations for both COVID-19-specific and non-COVID-19-specific tests include younger age {21–40 years: (3.61 [1.26–10.38]); 41–60 years: (4.49 [1.43–14.13])}, adherence to employer's health policy (2.94 [1.41–6.14]), being worried about contracting COVID-19 (2.95 [1.45– 5.99]), and during the transition (2.03 [1.02–4.06]) and mitigation (2.02 [1.03–3.97]) phases of the pandemic.ConclusionPatients' expectations for diagnostic tests during ED visits for uncomplicated URTI were dynamic across the COVID-19 pandemic phases. Expectations for COVID-19-specific diagnostic tests for ED visits for uncomplicated URTI were higher among younger individuals and those worried about contracting COVID-19 during the COVID-19 pandemic. Future studies are required to enhance public communications on the availability of diagnostic services in primary care and public education on self-management of emerging infectious diseases such as COVID-19.

Abstract Background The COVID-19 pandemic has changed the epidemiology of upper respiratory tract infections (URTI) and the disease profile of patients attending the emergency department (ED). Hence, we sought to explore the changes in ED physicians’ attitudes and behaviours in four EDs in Singapore. Methods We employed a sequential mixed-methods approach (quantitative survey followed by in-depth interviews). Principal component analysis was performed to derive latent factors, followed by multivariable logistic regression to explore the independent factors associated with high antibiotic prescribing. Interviews were analysed using the deductive-inductive-deductive framework. We derive five meta-inferences by integrating the quantitative and qualitative findings with an explanatory bidirectional framework. Results We obtained 560 (65.9%) valid responses from the survey and interviewed 50 physicians from various work experiences. ED physicians were twice as likely to report high antibiotic prescribing rates pre-COVID-19 pandemic than during the pandemic (AOR = 2.12, 95% CI 1.32 to 3.41, p = 0.002). Five meta-inferences were made by integrating the data: (1) Less pressure to prescribe antibiotics due to reduced patient demand and more patient education opportunities; (2) A higher proportion of ED physicians self-reported lower antibiotic prescribing rates during the COVID-19 pandemic but their perception of the overall outlook on antibiotic prescribing rates varied; (3) Physicians who were high antibiotic prescribers during the COVID-19 pandemic made less effort for prudent antibiotic prescribing as they were less concerned about antimicrobial resistance; (4) the COVID-19 pandemic did not change the factors that lowered the threshold for antibiotic prescribing; (5) the COVID-19 pandemic did not change the perception that the public's knowledge of antibiotics is poor. Conclusions Self-reported antibiotic prescribing rates decreased in the ED during the COVID-19 pandemic due to less pressure to prescribe antibiotics. The lessons and experiences learnt from the COVID-19 pandemic can be incorporated into public and medical education in the war against antimicrobial resistance going forward. Antibiotic use should also be monitored post-pandemic to assess if the changes are sustained.

Abstract Immunosenescence (age-related immune dysfunction) and inflamm-aging contribute to suboptimal immune responses in older adults to standard-dose influenza vaccines, which may be exacerbated in those with metabolic co-morbidities. We sought to investigate metabolic factors/predictors of influenza vaccine immune response in an older adult (age ≥65 years) cohort in Singapore, where influenza typically circulates year-round. The primary outcome for the DYNAMIC prospective cohort study was haemagglutination-inhibition titer (HAI) response to each of the trivalent inactivated influenza vaccine strains at day 28 (D28) compared to baseline (D0), as assessed by seroconversion and D28/D0 log2 HAI fold rise. Baseline blood samples were tested for total Vitamin D (25-(OH) D) levels. We enrolled 234 participants in June–Dec 2017. Two hundred twenty completed all study visits. The median age was 71 [IQR 68–75] years, 67 (30.5%) had diabetes mellitus (DM), and the median BMI was 24.9 [IQR 22.2–27.8] kg/m2. Median baseline totals 25-(OH) D was 29 [IQR: 21–29] ng/ml. Age, DM, obesity, and baseline 25-(OH) D were not associated with HAI fold rise in multivariable analysis. More recent prior influenza vaccination and higher baseline HAI titers were associated with lower HAI fold rise for influenza A/HK/H3N2. Physical activity was associated with a higher HAI fold rise for influenza A/HK/H3N2 in a dose-response relationship (p-test for trend = 0.015). Older adults with well-controlled metabolic co-morbidities retain HAI response to the influenza vaccine, and physical activity had a beneficial effect on immune response, particularly for influenza A/HK/H3N2.

Abstract We assessed the preferences and trade-offs for social interactions, incentives, and being traced by a digital contact tracing (DCT) tool post lockdown in Singapore by a discrete choice experiment (DCE) among 3839 visitors of a large public hospital in Singapore between July 2020 – February 2021. Respondents were sampled proportionately by gender and four age categories (21 – 80 years). The DCE questionnaire had three attributes (1. Social interactions, 2. Being traced by a DCT tool, 3. Incentives to use a DCT tool) and two levels each. Panel fixed conditional logit model was used to analyse the data. Respondents were more willing to trade being traced by a DCT tool for social interactions than incentives and unwilling to trade social interactions for incentives. The proportion of respondents preferring no incentives and could only be influenced by their family members increases with age. Among proponents of monetary incentives, the preferred median value for a month’s usage of DCT tools amounted to S$10 (USD7.25) and S$50 (USD36.20) for subsidies and lucky draw. In conclusion, DCE can be used to elicit profile-specific preferences to optimize the uptake of DCT tools during a pandemic. Social interactions are highly valued by the population, who are willing to trade them for being traced by a DCT tool during the COVID-19 pandemic. Although a small amount of incentive is sufficient to increase the satisfaction of using a DCT tool, incentives alone may not increase DCT tool uptake.

Carbapenemase-producing Enterobacterales cause healthcare-associated infections but modes of transmission are not well understood. Here, the authors find evidence of transmission without direct patient contact, indicating presence of undetected environmental reservoirs, whilst half of the transmission events are likely due to plasmid-mediated transmission.

ABSTRACT: Objectives: Following the emergence of the Delta variant of SARS-CoV-2 in Singapore, our hospital experienced a Delta-linked ward cluster. In this study, we review the enhanced strategies in preventing nosocomial transmission of COVID-19 following widespread community transmission of the Delta variant. Methods: We conducted a cohort study on exposures to unexpected COVID-19 cases for which contact tracing was initiated from June 2021 to October 2021. Strategies evaluated included upgraded personal protective equipment (PPE) and rostered routine testing (RRT) for staff and patients, surveillance of staff with acute respiratory illness (ARI), and expanded quarantining and testing for contacts of identified cases. Results: From 193 unexpected COVID-19 exposures, 2,573 staff, 542 patients, and 128 visitor contacts were traced. Four staff contacts subsequently had SARS-CoV-2 infection. Two were likely from exposure in community settings, whereas 2 had exposure to the same COVID-19 positive staff in the hospital, forming the only hospital cluster. One inpatient had a nosocomial infection, possibly from visitors. The SARS-CoV-2 detection rate among staff was 0.3% (of 11,200 staff) from biweekly RRT and 2.5% (of 3,675 staff) from ARI surveillance. Conclusion: Enhanced hospital measures, including upgraded PPE and RRT for staff and patients, staff sickness surveillance, and more rigorous management of contacts of COVID-19 cases, were likely to have reduced nosocomial transmission amid the Delta variant.

BackgroundThe misuse and overuse of antibiotics contribute to the acceleration of antimicrobial resistance (AMR), but public knowledge on appropriate antibiotic use and AMR remained low despite ongoing health promotion efforts. App gamification has gained traction in recent years for health promotion and to affect change in health behaviors. Hence, we developed an evidence-based serious game app “SteWARdS Antibiotic Defence” to educate the public on appropriate antibiotic use and AMR and address knowledge gaps. ObjectiveWe aim to evaluate the effectiveness of the “SteWARdS Antibiotic Defence” app in improving the knowledge of, attitude toward, and perception (KAP) of appropriate antibiotic use and AMR among the public. The primary objective is to assess the changes in KAP of antibiotic use and AMR in our participants, while the secondary objectives are to assess the extent of user engagement with the app and the level of user satisfaction in using the app. MethodsOur study is a parallel 2-armed randomized controlled trial with a 1:1 allocation. We plan to recruit 400 participants (patients or their caregivers) aged 18-65 years from government-funded primary care clinics in Singapore. Participants are randomized in blocks of 4 and into the intervention or control group. Participants in the intervention group are required to download the “SteWARdS Antibiotic Defence” app on their smartphones and complete a game quest within 2 weeks. Users will learn about appropriate antibiotic use and effective methods to recover from uncomplicated upper respiratory tract infections by interacting with the nonplayer characters and playing 3 minigames in the app. The control group will not receive any intervention. ResultsThe primary study outcome is the change in participants’ KAP toward antibiotic use and AMR 6-10 weeks post intervention or 6-10 weeks from baseline for the control group (web-based survey). We will also assess the knowledge level of participants immediately after the participant completes the game quest (in the app). The secondary study outcomes are the user engagement level (tracked by the app) and satisfaction level of playing the game (via the immediate postgame survey). The satisfaction survey will also collect participants’ feedback on the game app. ConclusionsOur proposed study provides a unique opportunity to assess the effectiveness of a serious game app in public health education. We anticipate possible ceiling effects and selection bias in our study and have planned to perform subgroup analyses to adjust for confounding factors. The app intervention will benefit a larger population if it is proven to be effective and acceptable to users. Trial RegistrationClinicalTrials.gov NCT05445414; https://clinicaltrials.gov/ct2/show/NCT05445414 International Registered Report Identifier (IRRID)DERR1-10.2196/45833

Objectives: In this study, we compared the performance of a rapid polymerase chain reaction (PCR) method in detecting carbapenemase-producing organisms (CPOs) and its impact on infection prevention and control (IPC) measures compared with a culture PCR method. Methods: All patients requiring CPO screening were included. Rectal swabs were collected with double rayon swabs (Copan 139C). They were simultaneously analyzed for the presence of CPOs using rapid PCR assay (Xpert Carba-R assay, Cepheid, Sunnyvale, CA) and a culture–PCR method (ChromID CARBA-SMART, bioMerieux, Marcy-l’Etoile, France). For CARBA-SMART, only colored colonies (ie, Enterobacterales) were evaluated for CPOs according to the prevailing institutional protocol. We tracked time to CPO detection. Using CPO positivity from either the rapid PCR or the culture PCR method as the gold standard, we calculated the sensitivity and specificity of both tests. We calculated the number of epidemiologically linked contacts generated when the first test results were known. We prospectively followed the ward census to identify the putative additional number of contacts generated by the later known result. Contacts were patients who shared the same ward (with overlapping time) as the CPO patients. Results: Between April 2019 and June 2020, culture PCR method detected CPOs in 316 (1.3%) of 24,514 samples (blaOXA48, N = 211; blaNDM, N = 51; blaIMI, N = 21; blaIMP, N = 10; blaKPC, N = 9; mixed genotypes, N = 14). The rapid PCR test detected CPOs in 605(2.5%) of 24,514 samples (blaOXA48, N = 266; blaNDM, N = 161; blaIMP, N = 99; blaVIM, N = 29; blaKPC, N = 15; mixed genotypes, N = 35). The sensitivity of direct PCR and culture PCR methods were 94.2% (95% CI, 92.1%–95.8%) and 43.5% (95% CI, 39.6%–47.4%), respectively. Both tests had 100% specificity. The median times to detection for the rapid PCR and culture PCR methods were 3–4 hours and 4 days, respectively. Compared with rapid PCR, the culture PCR method generated additional 7,415 contacts when it also tested positive for CPOs and an additional 23,135 contacts when it tested negative for CPOs. Conclusions: In our study, the rapid PCR test was more sensitive, identified CPO faster, and generated fewer epidemiologically linked contacts than the culture PCR method.

Objectives: In tertiary-care settings, up to 50% of patients are prescribed at least 1 antibiotic. However, patients are often not proactively provided with information nor involved in shared decisions regarding their antibiotic therapies. Understanding inpatients’ knowledge and the extent of their involvement in antibiotic therapy help reduce inappropriate or unnecessary antibiotic use. Methods: A cross-sectional survey was conducted from March to December 2021 in a 1,600-bed, adult, acute-care, tertiary-care hospital. Patients prescribed antibiotics for the past 1 week during their hospital stay were surveyed. Ten questions assessing patients’ knowledge of their antibiotic therapy and 3 questions adapted from the NHS Care Quality Commission Inpatient survey (2013) were included in the survey questionnaire. Results: Among the 323 patients surveyed, 88% knew that they had been given antibiotics, and 80% felt that it was important to be informed of the reason, 76% felt that it was important to be informed of side effects, 74% felt that it was important to be informed of duration, and 72% felt that it was important to be informed of dosing frequency. However, only 71% knew the dosing frequency, 54% knew the side effects, 37% knew the duration, and 13% knew the name of the antibiotic agent administered. Of those unaware of the antibiotic name, 59% had indicated their desire to know. Among those aware of their antibiotic therapy, 85% had trust in their doctors but only 42% felt that they always received answers to their questions on antibiotics in an understandable manner from their doctors. Furthermore, 41% felt that they were often or always not given enough time to question their doctors. To raise their awareness on antibiotic use, 73% of respondents felt that having protected time with the doctors to understand more about their antibiotic therapy would be effective. Conclusions: Most inpatients lacked knowledge of details of their antibiotic therapy, and fewer than half were involved in it. Allocation of protected time with doctors to understand their antibiotic therapy can be a potentially effective strategy to increase patient engagement to enhance hospital antibiotic stewardship efforts.

Abstract Background Since the last local case of diphtheria in 1992, there had not been any case in Singapore until an autochthonous case was reported in 2017. This fatal diphtheria case of a migrant worker raised concerns about the potential re-emergence of locally transmitted toxigenic diphtheria in Singapore. We conducted a seroprevalence study to assess the immunity levels to diphtheria among migrant workers in Singapore. Methods Residual sera from migrant workers who hailed from Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines were tested for anti-diphtheria toxoid immunoglobulin G (IgG) antibodies. These migrant workers previously participated in a survey between 2016 and 2019 and had provided blood samples as part of the survey procedure. Results A total of 2176 migrant workers were included in the study. Their overall mean age was 27.1 years (standard deviation 5.0), range was 20–43 years. The proportion having at least basic protection against diphtheria (antitoxin titres ≥ 0.01 IU/ml) ranged from 77.9% (95% confidence interval [CI] 72.8 – 82.3%) among migrant workers from Bangladesh to 96.7% (95% CI 92.5 – 98.6%) in those hailing from Malaysia. The proportion showing full protection (antitoxin titres ≥ 0.10 IU/ml) ranged from 10.1% (95% CI 6.5 – 15.4%) in Chinese workers to 23.0% (95% CI 17.1 – 30.3%) in Malaysian workers. There were no significant differences in the proportion with at least basic protection across birth cohorts, except for those from Bangladesh where the seroprevalence was significantly lower in younger migrant workers born after 1989. Conclusions The proportions having at least basic protection against diphtheria in migrant workers from five out of seven Asian countries (India, Indonesia, Malaysia, Myanmar and the Philippines) were higher than 85%, the threshold for diphtheria herd immunity. Seroprevalence surveys should be conducted periodically to assess the level of immunity against diphtheria and other vaccine preventable diseases in migrant worker population, so that appropriate interventions such as booster vaccination can be implemented proactively to prevent sporadic outbreaks.

Abstract Background In 2019, two clusters of measles cases were reported in migrant worker dormitories in Singapore. We conducted a seroprevalence study to measure the level of susceptibility to measles among migrant workers in Singapore. Methods Our study involved residual sera of migrant workers from seven Asian countries (Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines) who had participated in a survey between 2016 and 2019. Immunoglobulin G (IgG) antibody levels were first measured using a commercial enzyme-linked immunosorbent assay (ELISA) test kit. Those with equivocal or negative IgG results were further evaluated using plaque reduction neutralization test (PRNT). Results A total of 2234 migrant workers aged 20–49 years were included in the study. The overall prevalence of measles IgG antibodies among migrant workers from the seven Asian countries was 90.5% (95% confidence interval 89.2–91.6%). The country-specific seroprevalence ranged from 80.3 to 94.0%. The seroprevalence was significantly higher among migrant workers born in 1965–1989 than those born in 1990–1999 (95.3% vs. 86.6%, p

Abstract Background Singapore’s healthcare system presents an ideal context to learn from diverse public and private operational models and funding systems. Aim To explore processes underpinning decision-making for antibiotic prescribing, by considering doctors’ experiences in different primary care settings. Methods Thirty semi-structured interviews were conducted with 17 doctors working in publicly funded primary care clinics (polyclinics) and 13 general practitioners (GP) working in private practices (solo, small and large). Data were analysed using applied thematic analysis following realist principles, synthesised into a theoretical model, informing solutions to appropriate antibiotic prescribing. Results Given Singapore’s lack of national guidelines for antibiotic prescribing in primary care, practices are currently non-standardised. Themes contributing to optimal prescribing related first and foremost to personal valuing of reduction in antimicrobial resistance (AMR) which was enabled further by organisational culture creating and sustaining such values, and if patients were convinced of these too. Building trusting patient-doctor relationships, supported by reasonable patient loads among other factors were consistently observed to allow shared decision-making enabling optimal prescribing. Transparency and applying data to inform practice was a minority theme, nevertheless underpinning all levels of optimal care delivery. These themes are synthesised into the VALUE model proposed for guiding interventions to improve antibiotic prescribing practices. These should aim to reinforce intrapersonal V alues consistent with prioritising AMR reduction, and A ligning organisational culture to these by leveraging standardised guidelines and interpersonal intervention tools. Such interventions should account for the wider systemic constraints experienced in publicly funded high patient turnover institutions, or private clinics with transactional models of care. Thus, ultimately a focus on L iaison between patient and doctor is crucial. For instance, building in adequate consultation time and props as discussion aids, or quick turnover communication tools in time-constrained settings. Message consistency will ultimately improve trust, helping to enable shared decision-making. Lastly, U se of monitoring data to track and E valuate antibiotic prescribing using meaningful indicators, that account for the role of shared decision-making can also be leveraged for change. Conclusions These VALUE dimensions are recommended as potentially transferable to diverse contexts, and the model as implementation tool to be tested empirically and updated accordingly.

IntroductionShared decision-making (SDM) and trust building through continuity of care are known to play a pivotal role in improving appropriate antibiotic prescribing and use.ProblemHowever, less is known about how to effectively leverage these factors when present—or overcome them when not—to address community needs and improve patient liaison.MethodsWe addressed this question using a convergent parallel mixed-methods design. Focus group discussions (N = 13; August 2018–September 2020), were analyzed alongside a nationally-representative cross-sectional survey (N = 2004; November 2020–January 2021), in Singapore. Descriptive quantitative analyses and multivariable logistic regression were undertaken to examine antibiotic knowledge and factors associated with preference for SDM. Qualitative applied thematic analysis was integrated with these data to further explain the findings.FindingsPoor knowledge and misbeliefs on appropriate antibiotic use and antimicrobial resistance (AMR) were identified. For example, only 9% of the surveyed population understood that AMR occurs when the bacteria, not the human body, become resistant to antibiotics. Qualitative data corroborated the survey findings and suggested a shared value was placed on public education to avoid the fallout from resistant bacterial strains on current and future generations. This study also identified the opportunity to harness community trust in primary care doctors, who were described as highly valued educators for antibiotic use and AMR. Those who had trust in doctors were 75% more likely to prefer SDM (aOR 1.75, 95% CI 1.10–2.77, P = 0.017), especially adults aged ≥50 years who were receiving continued care with a regular doctor (aOR 1.83, 95% CI 1.18–2.86, P = 0.007). Continuity of care was observed to value-add SDM by building trusting relationships, though it was often absent in younger populations.ConclusionThis study highlights the long-term value-add of building on cultural capital pertaining to appropriate antibiotic use and AMR, by leveraging on the role of trust in doctors, desire for SDM and anchoring these in continuity of care when possible.RecommendationsUsing focused messaging and exploring alternative channels of communications such as annual check-ins or tele-consultations with a regular doctor, and emphasizing continuity of care across all age groups would help bridge the identified gaps.

Background: Tailored sexuality education for adolescents with intellectual and developmental disabilities is a crucial, yet unmet, need as this population is particularly at risk for sexual abuse and victimisation. However, there are no evidence-based interventions to specifically address this need. This paper presents the development of an intervention framework to address equity in sexuality education and support adolescents with intellectual and developmental disabilities to understand and provide sexual consent, a foundational aspect of sexuality education and sexual health. Methods: The Sexual Health Equity Project team used a Community-Based Participatory Research approach to develop a four-module sexual consent intervention for adolescents with intellectual and developmental disabilities. We leveraged a diverse, interdisciplinary team in a suburban Midwestern school district, and used Backward Design to create objectives and assessments which were rooted in findings from qualitative data by special education teachers. Results: The resulting sexual consent intervention, "Ask Me First--Choices," is comprised of four modules covering topics including definition of sexual consent; decision-making strategies and practice; communicating consent and refusal, identifying situations of consent and non-consent; and legal issues surrounding consent. Each module is divided into five components for content delivery: (1) introduction, (2) lecture, (3) supplemental activity, (4) assessment, and (5) conclusion. We detail the intervention's unique aspects, emphasising areas where we used Universal Design for Learning principles to support teachers' instruction and students' learning. Conclusion: Our efforts to create a sexual consent intervention directly address sexuality education equity issues. We offer commentary on our design process and decisions, as well as recommendations for future groups who want to develop sexual health interventions in similar contexts for students with intellectual and developmental disabilities. Next steps include further testing and validation of the sexual consent intervention to build the evidence-base of sexuality education for adolescents with intellectual and developmental disabilities.

Abstract Background Early diagnosis is crucial in securing optimal outcomes in the HIV care cascade. Recent HIV infection (RHI) serves as an indicator of early detection in the course of HIV infection. Surveillance of RHI is important in uncovering at-risk groups in which HIV transmission is ongoing. The study objectives are to estimate the proportion of RHI among persons newly-diagnosed in 2013–2017, and to elucidate epidemiological factors associated with RHI in Singapore. Methods As part of the National HIV Molecular Surveillance Programme, residual plasma samples of treatment-naïve HIV-1 positive individuals were tested using the biotinylated peptide-capture enzyme immunoassay with a cutoff of normalized optical density ≤ 0.8 for evidence of RHI. A recent infection testing algorithm was applied for the classification of RHI. We identified risk factors associated with RHI using logistic regression analyses. Results A total of 701 newly-diagnosed HIV-infected persons were included in the study. The median age at HIV diagnosis was 38 years (interquartile range, 28–51). The majority were men (94.2%), and sexual route was the predominant mode of HIV transmission (98.3%). Overall, 133/701 (19.0, 95% confidence interval [CI] 16.2–22.0%) were classified as RHI. The proportions of RHI in 2015 (31.1%) and 2017 (31.0%) were significantly higher than in 2014 (11.2%). A significantly higher proportion of men having sex with men (23.4, 95% CI 19.6–27.6%) had RHI compared with heterosexual men (11.1, 95% CI 7.6–15.9%). Independent factors associated with RHI were: age 15–24 years (adjusted odds ratio [aOR] 4.18, 95% CI 1.69–10.31) compared with ≥55 years; HIV diagnosis in 2015 (aOR 2.36, 95% CI 1.25–4.46) and 2017 (aOR 2.52, 95% CI 1.32–4.80) compared with 2013–2014; detection via voluntary testing (aOR 1.91, 95% CI 1.07–3.43) compared with medical care; and self-reported history of HIV test(s) prior to diagnosis (aOR 1.72, 95% CI 1.06–2.81). Conclusion Although there appears to be an increasing trend towards early diagnosis, persons with RHI remain a minority in Singapore. The strong associations observed between modifiable behaviors (voluntary testing and HIV testing history) and RHI highlight the importance of increasing the accessibility to HIV testing for at-risk groups.

Abstract Background Appropriate antibiotic prescribing is key to combating antimicrobial resistance. Upper respiratory tract infections (URTIs) are common reasons for emergency department (ED) visits and antibiotic use. Differentiating between bacterial and viral infections is not straightforward. We aim to provide an evidence-based clinical decision support tool for antibiotic prescribing using prediction models developed from local data. Methods Seven hundred-fifteen patients with uncomplicated URTI were recruited and analysed from Singapore’s busiest ED, Tan Tock Seng Hospital, from June 2016 to November 2018. Confirmatory tests were performed using the multiplex polymerase chain reaction (PCR) test for respiratory viruses and point-of-care test for C-reactive protein. Demographic, clinical and laboratory data were extracted from the hospital electronic medical records. Seventy percent of the data was used for training and the remaining 30% was used for validation. Decision trees, LASSO and logistic regression models were built to predict when antibiotics were not needed. Results The median age of the cohort was 36 years old, with 61.2% being male. Temperature and pulse rate were significant factors in all 3 models. The area under the receiver operating curve (AUC) on the validation set for the models were similar. (LASSO: 0.70 [95% CI: 0.62–0.77], logistic regression: 0.72 [95% CI: 0.65–0.79], decision tree: 0.67 [95% CI: 0.59–0.74]). Combining the results from all models, 58.3% of study participants would not need antibiotics. Conclusion The models can be easily deployed as a decision support tool to guide antibiotic prescribing in busy EDs.

BackgroundSingapore’s national digital contact-tracing (DCT) tool—TraceTogether—attained an above 70% uptake by December 2020 after a slew of measures. Sentiment analysis can help policymakers to assess public sentiments on the implementation of new policy measures in a short time, but there is a paucity of sentiment analysis studies on the usage of DCT tools. ObjectiveWe sought to understand the public’s knowledge of, concerns with, and sentiments on the use of TraceTogether over time and their preferences for the type of TraceTogether tool. MethodsWe conducted a cross-sectional survey at a large public hospital in Singapore after the COVID-19 lockdown, from July 2020 through February 2021. In total, 4097 respondents aged 21-80 years were sampled proportionately by sex and 4 age groups. The open-ended responses were processed and analyzed using natural language processing tools. We manually corrected the language and logic errors and replaced phrases with words available in the syuzhet sentiment library without altering the original meaning of the phrases. The sentiment scores were computed by summing the scores of all the tokens (phrases split into smaller units) in the phrase. Stopwords (prepositions and connectors) were removed, followed by implementing the bag-of-words model to calculate the bigram and trigram occurrence in the data set. Demographic and time filters were applied to segment the responses. ResultsRespondents’ knowledge of and concerns with TraceTogether changed from a focus on contact tracing and Bluetooth activation in July-August 2020 to QR code scanning and location check-ins in January-February 2021. Younger males had the highest TraceTogether uptake (24/40, 60%), while older females had the lowest uptake (8/34, 24%) in the first half of July 2020. This trend was reversed in mid-October after the announcement on mandatory TraceTogether check-ins at public venues. Although their TraceTogether uptake increased over time, older females continued to have lower sentiment scores. The mean sentiment scores were the lowest in January 2021 when the media reported that data collected by TraceTogether were used for criminal investigations. Smartphone apps were initially preferred over tokens, but the preference for the type of TraceTogether tool equalized over time as tokens became accessible to the whole population. The sentiments on token-related comments became more positive as the preference for tokens increased. ConclusionsThe public’s knowledge of and concerns with the use of a mandatory DCT tool varied with the national regulations and public communications over time with the evolution of the COVID-19 pandemic. Effective communications tailored to subpopulations and greater transparency in data handling will help allay public concerns with data misuse and improve trust in the authorities. Having alternative forms of the DCT tool can increase the uptake of and positive sentiments on DCT.

Abstract Background Streptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore. Methods Retrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design. Results We identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p 3. Conclusion Patients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.

Understanding the change in intention for influenza vaccine among health-care workers (HCWs) is important to increase influenza vaccination uptake. We aimed to investigate the psychosocial beliefs associated with a change in the intention for influenza vaccine. An anonymous cross-sectional survey was distributed to tertiary hospital HCWs in 2016. Of 3007 HCWs, 70% were compliant (vaccinated, with an intention to revaccinate), 8% were resistant (unvaccinated, without intention to vaccinate), 10% had positive change (unvaccinated, but with intention) and 12% had negative change (vaccinated, but without intention). Across HCW groups, medical staff had both the highest proportion receiving all influenza vaccinations in the last 5 years (101, 28.4%), as well as the highest proportion who had never received vaccination (41, 11.5%). With increasing age, HCWs were less likely to have a negative (p = .02) or positive change (p = .06) in intention, compared to the vaccine-resistant group. HCWs were more likely to be compliant or have a positive change in intention to receive influenza vaccine, if they perceived the vaccine as effective, safe, or had a higher frequency of influenza vaccination in the last 5 years (all with p < .05). HCWs who were medical staff, who believed that side effects of the vaccine were common, or had worked for 6 to 10 years (vs 5 years or less) were less likely to be compliant (all with p < .05). In conclusion, older HCWs were more likely to maintain the status quo in their behavior toward influenza vaccination. Influenza vaccination strategies should place emphasis on vaccine effectiveness and safety.

Objective To assess the temporal trend and identify risk factors associated with the absence of previous HIV testing prior to their diagnosis among HIV-positive persons in Singapore.Study design Cross-sectional.Setting and participants We analysed data of HIV-positive persons infected via sexual transmission, who were notified to the National HIV Registry in 2012–2017.Outcomes Epidemiological factors associated with the absence of HIV testing prior to diagnosis were determined separately for two groups of HIV-positive persons: early and late stages of HIV infection at diagnosis.Results 2188 HIV-positive persons with information on HIV testing history and CD4 cell count were included in the study. The median age at HIV diagnosis was 40 years (IQR 30–51). Nearly half (45.1%) had never been tested for HIV prior to their diagnosis. The most common reason cited for no previous HIV testing was ‘not necessary to test’ (73.7%). The proportion diagnosed at late-stage HIV infection was significantly higher among HIV-positive persons who had never been tested for HIV (63.9%) compared with those who had undergone previous HIV tests (29.0%). Common risk factors associated with no previous HIV testing in multivariable logistic regression analysis stratified by stage of HIV infection were: older age at HIV diagnosis, lower educational level, detection via medical care and HIV infection via heterosexual transmission. In the stratified analysis for persons diagnosed at early-stage of HIV infection, in addition to the four risk factors, women and those of Malay ethnicity were also less likely to have previous HIV testing prior to their diagnosis.Conclusion Targeted prevention efforts and strategies are needed to raise the level of awareness of HIV/AIDS and to encourage early and regular screening among the at-risk groups by making HIV testing more accessible.

Background: Poor knowledge of antibiotic use drives poor antibiotic practices, but little is known about the influence of health information orientation (HIO) on knowledge of antibiotic use in the general public. Methods: We conducted a nationally-representative population-wide cross-sectional study (November 2020–January 2021), on a proportionately stratified random sample of 2004 Singapore residents aged ≥21 years. Multivariable logistic regression analysis was performed to assess the association between HIO and knowledge of antibiotic use. Results: Forty percent of respondents had low-levels of HIO (LL-HIO); they tended to be younger, not currently married, and did not have family/friends working in the healthcare sector. Respondents with LL-HIO (aOR 1.82, 95% CI 1.32–2.51, p < 0.001) were 82% more likely to have poor knowledge of antibiotic use. In particular, older adults aged ≥50 years with LL-HIO (aOR 1.81, 95% CI [1.32–2.51], p < 0.001) were much more likely to have poor knowledge than their HL-HIO counterparts. They were also less likely to use the Internet to seek health information and had poor eHealth efficacy. Conclusion: LL-HIO is independently associated with poor knowledge of antibiotic use. Educational strategies on antibiotic use should disseminate a consistent message through both online and offline platforms, involving traditional and non-traditional healthcare and non-healthcare influencers.

Abstract Background A growing number of studies observe associations between the amount of green space around a mother’s home and positive birth outcomes; however, the robustness of this association and potential pathways of action remain unclear. Objectives To examine associations between mother’s residential green space and term birth weight within the Canadian Healthy Infant Longitudinal Development (CHILD) study and examine specific hypothesized pathways. Methods We examined 2510 births located in Vancouver, Edmonton, Winnipeg, and Toronto Canada. Green space was estimated around mother’s residences during pregnancy using Landsat 30 m normalized difference vegetation index (NDVI). We examined hypothesized pathways of: (1) reduction of environmental exposure; (2) built environment features promoting physical activity; (3) psychosocial conditions; and (4) psychological influences. Linear regression was used to assess associations between green space and term birth weight adjusting first for a comprehensive set of confounding factors and then incrementally for pathway variables. Results Fully adjusted models showed non-statistically significant increases in term birth weight with increasing green space. For example, a 0.1 increase in NDVI within 500 m was associated with a 21.5 g (95% CI − 4.6, 47.7) increase in term birth weight. Associations varied by city and were most robust for high-density locations. For the two largest cities (Vancouver and Toronto), we observed an increase in birth weight of 41.2 g (95% CI 7.8, 74.6) for a 0.1 increase in NDVI within 500 m. We did not observe substantial reductions in the green space effect on birth weight when adjusting for pathway variables. Conclusion Our results highlight the need to further characterize the interactions between green space, urban density and climate related factors as well as the pathways linking residential green space to birth outcomes.

The purpose of this study was to investigate the relationship between different levels of physical activity (light, moderate, and vigorous), physical health, happiness, and depression among older adults with diabetes. Using data from the National Social Life, Health and Aging Project (NSHAP) Wave 3, the results indicate that moderate and/or vigorous physical activity is more effective than light physical activity for promoting physical health and happiness and lowering depression of older adults with diabetes. This study suggests that activity professionals and therapists working with older adults with diabetes need to encourage their participation in physical activity as well as adjust a level of physical activity intensity that is tailored to participants’ needs and expectations.

Dengue virus and Zika virus coexist in tropical regions in Asia where healthcare resources are limited; differentiating the 2 viruses is challenging. We showed in a case–control discovery cohort, and replicated in a validation cohort, that the diagnostic indices of conjunctivitis, platelet count, and monocyte count reliably distinguished between these viruses.

Abstract Background The first autochthonous Zika virus (ZIKV) outbreak in Singapore was detected in August 2016. We report an analysis of the correlation of clinical illness with viremia and laboratory parameters in this Asian cohort. Methods We conducted a prospective longitudinal cohort study of patients with a positive blood ZIKV polymerase chain reaction (PCR) result who were admitted to Tan Tock Seng Hospital, Singapore, for isolation and management. Results We included 40 patients in our study. Rash was present in all patients, while 80% (32/40) had fever, 62.5% (25/40) myalgia, 60% (24/40) conjunctivitis and 38% (15/40) arthralgia. The median duration of viremia was 3.5 days (IQR: 3–5 days). Patients with viremia of ≥4 days were more likely to have prolonged fever compared to those with viremia of less than 4 days (95% versus 63%, p = 0.01), but had no significant correlation with other clinical signs and symptoms, or laboratory investigations. However, 21 patients (53%) had hypokalemia despite the absence of gastrointestinal symptoms. Conclusion Although fever correlated with duration of viremia, 30% of patients remained viremic despite defervescence. Laboratory abnormalities such as leukopenia or thrombocytopenia were not prominent in this cohort but about half the patients were noted to have hypokalemia.

Objectives: Understanding factors influencing inappropriate antibiotic use can guide the design of interventions to improve antibiotic practices and reduce antimicrobial resistance (AMR). Methods: A nationally representative cross-sectional survey (N = 2004) was conducted between November 2020 and January 2021. Knowledge of antibiotic use and AMR using the World Health Organization’s Multi-Country AMR Survey questionnaire, and antibiotic practices were examined. Multivariable logistic regression was performed to identify factors associated with inappropriate antibiotic use and examine effect measure modifications. Results: After adjusting for potential confounding, poor knowledge of antibiotic use was associated with a 3x increased odds of inappropriate antibiotic use in adults aged ≥50 years (aOR 3.11, 95% CI [2.24–4.32]), 5× increased odds in those aged 35–49 years (aOR 4.88, 95% CI [3.32–7.16]), and 7× increased odds in those aged 21–34 years (aOR 6.58, 95% CI [4.19–10.33]). While there was no statistically significant association in adults aged ≥50 years, poor knowledge of AMR increased the odds of inappropriate antibiotic use by 4 times in adults aged 35–49 years (aOR 3.73, 95% CI [1.53–9.11]) and 5 times in those aged 21–34 years (aOR 4.90, 95% CI [1.84–13.02]). Conclusions: Targeted educational interventions for specific age groups are needed in conjunction with empowering the public with knowledge of antibiotic use and AMR.

Antimicrobial stewardship programmes (ASPs) in hospitals are predominantly led by specific ASP physicians and pharmacists. Limited studies have been conducted to appreciate non-ASP-trained hospital pharmacists’ perspectives on their roles in antimicrobial stewardship. Focus group discussions (FGDs) were conducted with 74 pharmacists, purposively sampled from the 3 largest acute-care public hospitals in Singapore, to explore facilitators and barriers faced by them in antimicrobial stewardship. Applied thematic analysis was conducted and codes were categorised using the social–ecological model (SEM). At the intrapersonal level, pharmacists identified themselves as reviewers for drug safety before dispensing, confining to a restricted advisory role due to lack of clinical knowledge, experience, and empowerment to contribute actively to physicians’ prescribing decisions. At the interpersonal level, pharmacists expressed difficulties conveying their opinions and recommendations on antibiotic therapy to physicians despite frequent communications, but they assumed critical roles as educators for patients and their caregivers on proper antibiotic use. At the organisational level, in-house antibiotic guidelines supported pharmacists’ antibiotic interventions and recommendations. At the community level, pharmacists were motivated to improve low public awareness and knowledge on antibiotic use and antimicrobial resistance. These findings provide important insights into the gaps to be addressed in order to harness the untapped potential of hospital pharmacists and fully engage them in antimicrobial stewardship.

Singapore experienced its first documented Zika virus outbreak in 2016. We identified clinical and laboratory parameters that increase the probability for Zika or dengue virus infection. Early during the illness, combinations of key parameters obtained through clinical assessment and hematologic tests can help distinguish between these infections.

Abstract Background Hospital usage and service demand during an Infectious Disease (ID) outbreak can tax the health system in different ways. Herein we conceptualize hospital surge elements, and lessons learnt from such events, to help build appropriately matched responses to future ID surge threats. Methods We used the Interpretive Descriptive qualitative approach. Interviews (n = 35) were conducted with governance and public health specialists; hospital based staff; and General Practitioners. Key policy literature in tandem with the interview data were used to iteratively generate a Hospital ID Surge framework. We anchored our narrative account within this framework, which is used to structure our analysis. Results A spectrum of surge threats from combinations of capacity (for crowding) and capability (for treatment complexity) demands were identified. Starting with the Pyramid scenario, or an influx of high screening rates flooding Emergency Departments, alongside fewer and manageable admissions; the Reverse-Pyramid occurs when few cases are screened and admitted but those that are, are complex; during a ‘Black’ scenario, the system is overburdened by both crowding and complexity. The Singapore hospital system is highly adapted to crowding, functioning remarkably well at constant near-full capacity in Peacetime and resilient to Endemic surges. We catalogue 26 strategies from lessons learnt relating to staffing, space, supplies and systems, crystalizing institutional memory. The DECIDE model advocates linking these strategies to types of surge threats and offers a step-by-step guide for coordinating outbreak planning and response. Conclusions Lack of a shared definition and decision making of surge threats had rendered the procedures somewhat duplicative. This burden was paradoxically exacerbated by a health system that highly prizes planning and forward thinking, but worked largely in silo until an ID crisis hit. Many such lessons can be put into play to further strengthen our current hospital governance and adapted to more diverse settings.

An outbreak of invasive group B Streptococcus (GBS) disease occurred in Singapore in mid-2015. We conducted a case–control study of 22 adults with invasive GBS infections during June 21–November 21, 2015. Consumption of raw fish was strongly associated with invasive sequence type 283 infections, but not with non–sequence type 283 infections.

We evaluated performance of 5 case definitions for Zika virus disease surveillance in a human cohort during an outbreak in Singapore, August 26–September 5, 2016. Because laboratory tests are largely inaccessible, use of case definitions that include rash as a required clinical feature are useful in identifying this disease.

Objectives: To describe the clinical features, treatments, outcomes, and subtype prevalence of cryptococcosis in Singapore. Methods: All patients with laboratory confirmed cryptococcal infections admitted from 1999 to 2007 to a teaching hospital in Singapore were reviewed retrospectively. Identification and molecular types of Cryptococcus neoformans variants and Cryptococcus gattii were determined by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Serotypes were inferred with a multiplex PCR method. Results: Of 62 patients with cryptococcosis, C. neoformans var. grubii was the predominant subtype (in 95%), affecting mainly immunocompromised hosts (91%) with HIV infection (80%). Patients with HIV were younger (median age 36.5 vs. 49.5 years, p = 0.006) and less likely to present with an altered mental status (14% vs. 50%, p = 0.013). In contrast, delayed treatment (median 7 days vs. 2 days, p = 0.03), pulmonary involvement (58% vs. 14%, p = 0.03), and initial treatment with fluconazole (25% vs. 2%, p = 0.02) were more common in HIV-negative patients. C. gattii was uncommon, affecting only three patients, all of whom were immunocompetent and had disseminated disease with pulmonary and neurological involvement. All C. gattii were RFLP type VG II, serotype B and all C. neoformans var. grubii were RFLP type VN I, serotype A, except for one that was RFLP type VN II. Conclusion: C. neoformans var. grubii, subtype VN I, was the predominant subtype in Singapore, infecting younger, mainly immunocompromised hosts with HIV. C. gattii was uncommon, causing pulmonary manifestations in older, immunocompetent patients and were RFLP type VG II.

This study investigated PhD students’ conceptions of writing and how they saw themselves as writers. The Writing Process Questionnaire was created to analyse PhD students’ ideas of academic writing. In addition, it was of interest, what the relation between conceptions of writing and the PhD students’ well-being was. The participants were 669 PhD students from a major Finnish university who volunteered to fill in a questionnaire. The present study covered scales for measuring six distinct theoretical constructs that were created by forming sum variables of 26 questions: Blocks, Procrastination, Perfectionism, Innate ability, Knowledge transforming, and Productivity. Confirmatory factor analysis (CFA) was used to verify the six-dimension construct. Exhaustion, stress, anxiety and lack of interest all correlated positively with Blocks, Procrastination, and Perfectionism, and negatively with Productivity. Confirmatory factor analysis conducted by LISREL confirmed the six-factor structure of the writing scale. In conclusion, there is good evidence that the questionnaire is a reliable and valid tool, and it captures some essential aspectsof academic writing process and its emotional dimensions.

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are a common cause of bacteraemia in endemic countries and may be associated with high mortality; carbapenems are considered the drug of choice. Limited data suggest piperacillin-tazobactam could be equally effective. We aimed to compare 30-day mortality of patients treated empirically with piperacillin-tazobactam versus a carbapenem in a multi-centre retrospective cohort study in Singapore. Only patients with active empiric monotherapy with piperacillin-tazobactam or a carbapenem were included. A propensity score for empiric carbapenem therapy was derived and an adjusted multivariate analysis of mortality was conducted. A total of 394 patients had ESBL-Escherichia.coli and ESBL-Klebsiella pneumoniae bacteraemia of which 23.1% were community acquired cases. One hundred and fifty-one received initial active monotherapy comprising piperacillin-tazobactam (n = 94) or a carbapenem (n = 57). Patients who received carbapenems were less likely to have health-care associated risk factors and have an unknown source of bacteraemia, but were more likely to have a urinary source. Thirty-day mortality was comparable between those who received empiric piperacillin-tazobactam and a carbapenem (29 [30.9%] vs. 17 [29.8%]), P = 0.89). Those who received empiric piperacillin-tazobactam had a lower 30-day acquisition of multi-drug resistant and fungal infections (7 [7.4%] vs. 14 [24.6%]), P

An oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus evolved and emerged from zero to 52% of detectable virus within 48 hours of a patient’s exposure to oseltamivir. Phylogenetic analysis and data gathered by pyrosequencing and cloning directly on clinical samples suggest that the mutant emerged de novo.

We describe incidence and risk factors for pandemic (H1N1) 2009 virus infection in healthcare personnel during the June–September 2009 epidemic in Singapore. Personnel contributed 3 serologic samples during June–October 2009, with seroconversion defined as a >4-fold increase in hemagglutination inhibition titers to pandemic (H1N1) 2009. Of 531 participants, 35 showed evidence of seroconversion. Seroconversion rates were highest in nurses (28/290) and lowest in allied health staff (2/116). Significant risk factors on multivariate analysis were being a nurse (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] 1.0–19.6) and working in pandemic (H1N1) 2009 isolation wards (aOR 4.5, 95% CI 1.3–15.6). Contact with pandemic (H1N1) 2009–infected colleagues (aOR 2.5, 95% CI 0.9–6.6) and larger household size (aOR 1.2, 95% CI 1.0–1.4) were of borderline significance. Our study suggests that seroconversion was associated with occupational and nonoccupational risk factors.

In June 2009, during Singapore’s pandemic influenza plan containment phase, pandemic (H1N1) 2009 was introduced into the country through imported cases. To understand how travel patterns affected the initial outbreak, we examined epidemiologic and travel data for the first 116 case-patients admitted to Tan Tock Seng Hospital, Singapore, with travel-associated infection. Sixty-one percent and 54% of patients, respectively, met US Centers for Disease Control and Prevention and World Health Organization temperature criteria for influenza-like illness. One fourth of the case-patients traveled after illness onset, and 15% became ill while traveling. Regions of exposure for imported infections changed rapidly; case-patients initially arrived from North America, followed by Australasia and Southeast Asia. Case-patients on longer flights were more likely to become ill before arrival; those with shorter flights tended to become ill after arrival. Thermal scanners detected fevers in 12% of the arriving case-patients, resulting in a shorter time to isolation.