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The article focuses on assessing burnout, anxiety, and depression among healthcare workers (HCWs) in Singapore during the early COVID-19 period. Topics include the impact of lockdown measures, prior experience with infectious disease outbreaks, and job-related perceptions on HCW psychological outcomes. It reports that psychological morbidity rates were comparable to those in China and Singapore.

Introduction: Migrant workers comprise about one-fifth of Singapore's resident population and form a substantial and vital component of the nation's workforce. However, limited data is available regarding the barriers that migrant workers face in accessing healthcare from the healthcare providers' perspective.Methods: We conducted a survey on doctors working in four restructured hospitals in Singapore, to assess what they perceived to be barriers faced by migrant workers in accessing healthcare. We also assessed the doctors' understanding of migrant-health-related policies in Singapore.Results: A total of 427 survey responses were collected. Most respondents were senior doctors (senior residents or consultants) who had been practising medicine for a median of ten years. Among doctors, the most common perceived barriers to migrant workers accessing healthcare were related to culture/language (92.3%) and finances (healthcare cost) (81.0%). Of the six questions asked pertaining to migrant healthcare policy in Singapore, the respondents achieved a median of four correctly answered questions (interquartile range 3-5), and about 55% were unaware or unsure of available resources for migrant workers.Conclusion: Our study identified healthcare providers' perceived barriers to the delivery of healthcare to migrant workers, which corroborate previously published data reported by migrant workers themselves. Further efforts should be directed towards diminishing these barriers and increasing the literacy of migrant health among healthcare workers. [ABSTRACT FROM AUTHOR]

• Cases of COVID-19 may be housed outside isolation wards prior to detection. • A bundle of infrastructural enhancements, improved PPE, and social distancing was implemented. • Of 253 staff close-contacts and 45 patient close-contacts of 28 index cases, 1 patient contact tested positive. • Environmental sampling was positive for SARS-CoV-2 in 5 out of 28 cases. • An infection control bundle mitigated COVID-19 transmission in a general ward setting. During an ongoing outbreak of COVID-19, unsuspected cases may be housed outside of dedicated isolation wards. At a Singaporean tertiary hospital, individuals with clinical syndromes compatible with COVID-19 but no epidemiologic risk were placed in cohorted general wards for COVID-19 testing. To mitigate risk, an infection control bundle was implemented comprising infrastructural enhancements, improved personal protective equipment, and social distancing. We assessed the impact on environmental contamination and transmission. Upon detection of a case of COVID-19 in the dedicated general ward, patients and health care workers (HCWs) contacts were identified. All patient and staff close-contacts were placed on 14-day phone surveillance and followed up for 28 days; symptomatic contacts were tested. Environmental samples were also obtained. Over a 3-month period, 28 unsuspected cases of COVID-19 were contained in the dedicated general ward. In 5 of the 28 cases, sampling of the patient's environment yielded SARS-CoV-2; index cases who required supplemental oxygen had higher odds of environmental contamination (P =.01). A total of 253 staff close-contacts and 45 patient close-contacts were identified; only 3 HCWs (1.2%, 3/253) required quarantine. On 28-day follow-up, no patient-to-HCW transmission was documented; only 1 symptomatic patient close-contact tested positive. Our institution successfully implemented an intervention bundle to mitigate COVID-19 transmission in a multibedded cohorted general ward setting. [ABSTRACT FROM AUTHOR]

Coronavirus disease-19 (COVID-19) is a pathogen that has shown an ability for sustained community transmission. To ensure utmost safety, radiology services will need to adapt to this disease in the coming months and possibly years ahead. This will include learning how to perform radiographs and CT in a safe and sustainable manner. Due to the risk of nosocomial spread of disease, the judicious use and implementation of strict infection protocols is paramount to limit healthcare worker and patient transmission. Between 28 January 2020 and 8 June 2020, our institution performed 12,034 radiographs and 178 CT scans for suspected or confirmed COVID-19 patients. As of 8 June 2020, there have been no documented instances of healthcare staff acquiring COVID-19 during the course of work. In this article, we present the indications and operational considerations used by our institution to safely image patients with suspected or confirmed COVID-19. Alternative practices for imaging radiographs are also discussed. [ABSTRACT FROM AUTHOR]

Background Platelet transfusion is common in dengue patients with thrombocytopenia. We previously showed in a randomized clinical trial that prophylactic platelet transfusion did not reduce clinical bleeding. In this study, we aimed to characterize the predictors and clinical outcomes of poor platelet recovery in transfused and nontransfused participants. Methods We analyzed patients from the Adult Dengue Platelet Study with laboratory-confirmed dengue with ≤20 000 platelets/μL and without persistent mild bleeding or any severe bleeding in a post hoc analysis. Poor platelet recovery was defined as a platelet count of ≤20 000/μL on Day 2. We recruited 372 participants from 5 acute care hospitals located in Singapore and Malaysia between 29 April 2010 and 9 December 2014. Of these, 188 were randomly assigned to the transfusion group and 184 to the control group. Results Of 360 patients, 158 had poor platelet recovery. Age, white cell count, and day of illness at study enrollment were significant predictors of poor platelet recovery after adjustment for baseline characteristics and platelet transfusion. Patients with poor platelet recovery had longer hospitalizations but no significant difference in other clinical outcomes, regardless of transfusion. We found a significant interaction between platelet recovery and transfusion; patients with poor platelet recovery were more likely to bleed if given a prophylactic platelet transfusion (odds ratio 2.34, 95% confidence interval 1.18–4.63). Conclusions Dengue patients with thrombocytopenia who were older or presented earlier and with lower white cell counts were more likely to have poor platelet recovery. In patients with poor platelet recovery, platelet transfusion does not improve outcomes and may actually increase the risk of bleeding. The mechanisms of poor platelet recovery need to be determined. Clinical Trials Registration NCT01030211. [ABSTRACT FROM AUTHOR]

To the Editor: Nordmann et al. (1) raised concern over the global spread of carbapenemase-producing Enterobacteriaceae. In their article, they called attention to the oxacillinase-48 (OXA-48) type carbapenemases because bacteria [...]

CELADEN was a randomized placebo-controlled trial of 50 patients with confirmed dengue fever to evaluate the efficacy and safety of celgosivir (A study registered at ClinicalTrials.gov, number NCT01619969). Celgosivir was given as a 400 mg loading dose and 200 mg bid (twice a day) over 5 days. Replication competent virus was measured by plaque assay and compared to reverse transcription quantitative PCR (qPCR) of viral RNA. Pharmacokinetics (PK) correlations with viremia, immunological profiling, next generation sequence (NGS) analysis and hematological data were evaluated as exploratory endpoints here to identify possible signals of pharmacological activity. Viremia by plaque assay strongly correlated with qPCR during the first four days. Immunological profiling demonstrated a qualitative shift in T helper cell profile during the course of infection. NGS analysis did not reveal any prominent signature that could be associated with drug treatment; however the phylogenetic spread of patients’ isolates underlines the importance of strain variability that may potentially confound interpretation of dengue drug trials conducted during different outbreaks and in different countries. Celgosivir rapidly converted to castanospermine (Cast) with mean peak and trough concentrations of 5727 ng/mL (30.2 μM) and 430 ng/mL (2.3 μM), respectively and cleared with a half-life of 2.5 (± 0.6) hr. Mean viral log reduction between day 2 and 4 (VLR2-4) was significantly greater in secondary dengue than primary dengue (p = 0.002). VLR2-4 did not correlate with drug AUC but showed a trend of greater response with increasing Cmin. PK modeling identified dosing regimens predicted to achieve 2.4 to 4.5 times higher Cmin. than in the CELADEN trial for only 13% to 33% increase in overall dose. A small, non-statistical trend towards better outcome on platelet nadir and difference between maximum and minimum hematocrit was observed in celgosivir-treated patients with secondary dengue infection. Optimization of the dosing regimen and patient stratification may enhance the ability of a clinical trial to demonstrate celgosivir activity in treating dengue fever based on hematological endpoints. A new clinical trial with a revised dosing regimen is slated to start in 2016 (NCT02569827). Furthermore celgosivir’s potential value for treatment of other flaviruses such as Zika virus should be investigated urgently. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Epidemic viral diseases have become more prevalent.. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies. Design: In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, we propose a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. We hypothesize that cross-reactive antibodies impact antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. We will structure an open-label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies. The clinical materials obtained in the trial will drive basic laboratory investigations directed at elucidating how heterologous antibody affect vaccination at the molecular level. YF neutralizing antibody titer will be measured using plaque reduction neutralization test against the vaccine strain YF17D. Innate immune response will be characterized genetically using either microarray or digital PCR (or both). The innate immune response will also be characterized at the protein and metabolite level using Luminex bead technology and lipidomic/metabolomic approaches. Discussion: This proposed study represents one of the first to examine the role of cross-reactive antibodies in modulating immune responses to vaccines, the findings of which may re-shape vaccination strategy. [ABSTRACT FROM AUTHOR]

Keywords: Anosmia; Ageusia; COVID-19 EN Anosmia Ageusia COVID-19 2389 2390 2 07/07/20 20200801 NES 200801 This comment refers to the article available online at 10.1007/s00405-020-05965-1. However, while a large proportion of COVID-19 patients had OTD, [[1]-[3]] the actual specificity as a criterion for screening suspected COVID-19 cases is unknown, as other viral infections may also cause OTD. Other studies have reported patients presenting with acute anosmia with or without upper respiratory tract symptoms, [[4]] but not all patients were tested for COVID-19 [[4]]. [Extracted from the article]

Central nervous system (CNS) infections cause substantial morbidity and mortality worldwide, with mounting concern about new and emerging neurologic infections. Stratifying etiologies based on initial clinical and laboratory data would facilitate etiology-based treatment rather than relying on empirical treatment. Here, we report the epidemiology and clinical outcomes of patients with CNS infections from a prospective surveillance study that took place between 2013 and 2016 in Singapore. Using multiple correspondence analysis and random forest, we analyzed the link between clinical presentation, laboratory results, outcome and etiology. Of 199 patients, etiology was identified as infectious in 110 (55.3%, 95%-CI 48.3–62.0), immune-mediated in 10 (5.0%, 95%-CI 2.8–9.0), and unknown in 79 patients (39.7%, 95%-CI 33.2–46.6). The initial presenting clinical features were associated with the prognosis at 2 weeks, while laboratory-related parameters were related to the etiology of CNS disease. The parameters measured were helpful to stratify etiologies in broad categories, but were not able to discriminate completely between all the etiologies. Our results suggest that while prognosis of CNS is clearly related to the initial clinical presentation, pinpointing etiology remains challenging. Bio-computational methods which identify patterns in complex datasets may help to supplement CNS infection diagnostic and prognostic decisions. [ABSTRACT FROM AUTHOR]

• Good syndrome (GS) is a rare acquired immunodeficiency. • Relapsing bacterial and viral infections are common in GS. • Relapsing COVID-19 infection has not been previously reported in GS. • We report a case of GS manifesting as relapsing COVID-19 infection. Good syndrome (GS) is a rare acquired immunodeficiency disease characterized by the presence of thymoma with combined B and T cell immunodeficiency in adults. Recurrent bacterial infections, particularly sinopulmonary infections caused by encapsulated bacteria, remain the most common infective presentation of GS; however, relapsing viral infections have also been reported, likely due to impaired T cell-mediated immunity. Relapsing COVID-19 infection, however, has not been previously reported as a manifestation of GS. We present two cases of relapsing COVID-19 infection in patients with GS; in one case, relapsing COVID-19 was the first manifestation of newly diagnosed GS. [ABSTRACT FROM AUTHOR]

Phenomenon: Medical Student Portfolios (MSP)s allow medical students to reflect and better appreciate their clinical, research and academic experiences which promotes their individual personal and professional development. However, differences in adoption rate, content design and practice setting create significant variability in their employ. With MSPs increasingly used to evaluate professional competencies and the student's professional identity formation (PIF), this has become an area of concern. Approach: We adopt Krishna's Systematic Evidence-Based Approach to carry out a Systematic Scoping Review (SSR in SEBA) on MSPs. The structured search process of six databases, concurrent use of thematic and content analysis in the Split Approach and comparisons of the themes and categories with the tabulated summaries of included articles in the Jigsaw Perspective and Funnelling Process offers enhanced transparency and reproducibility to this review. Findings: The research team retrieved 14501 abstracts, reviewed 779 full-text articles and included 96 articles. Similarities between the themes, categories and tabulated summaries allowed the identification of the following funnelled domains: Purpose of MSPs, Content and structure of MSPs, Strengths and limitations of MSPs, Methods to improve MSPs, and Use of E-portfolios. Insights: Variability in the employ of MSPs arise as a result of a failure to recognise its different roles and uses. Here we propose additional roles of MSPs, in particular, building on a consistent set of content materials and assessments of milestones called micro-competencies. Whislt generalised micro-competencies assess achievement of general milestones expected of all medical students, personalised micro-competencies record attainment of particular skills, knowledge and attitudes balanced against the medical student's abilities, context and needs. This combination of micro-competencies in a consistent framework promises a holistic, authentic and longitudinal perspective of the medical student's development and maturing PIF. [ABSTRACT FROM AUTHOR]

Background: Heralded as a teaching, assessment and reflective tool, and increasingly as a longitudinal and holistic perspective of the educator's development, medical educator's portfolios (MEP)s are increasingly employed to evaluate progress, assess for promotions and career switches, used as a reflective tool and as a means of curating educational activities. However, despite its blossoming role, there is significant dissonance in the content and structure of MEPs. As such, a systematic scoping review (SSR) is proposed to identify what is known of MEPs and its contents. Methods: Krishna's Systematic Evidenced Based Approach (SEBA) was adopted to structure this SSR in SEBA of MEPs. SEBA's constructivist approach and relativist lens allow data from a variety of sources to be considered to paint a holistic picture of available information on MEPs. Results: From the 12 360 abstracts reviewed, 768 full text articles were evaluated, and 79 articles were included. Concurrent thematic and content analysis revealed similar themes and categories including: (1) Definition and Functions of MEPs, (2) Implementing and Assessing MEPs, (3) Strengths and limitations of MEPs and (4) electronic MEPs. Discussion: This SSR in SEBA proffers a novel 5-staged evidence-based approach to constructing MEPs which allows for consistent application and assessment of MEPs. This 5-stage approach pivots on assessing and verifying the achievement of developmental milestones or 'micro-competencies' that facilitate micro-credentialling and effective evaluation of a medical educator's development and entrust-ability. This allows MEPs to be used as a reflective and collaborative tool and a basis for career planning. [ABSTRACT FROM AUTHOR]

Background: Medical professionalism enhances doctor-patient relationships and advances patient-centric care. However, despite its pivotal role, the concept of medical professionalism remains diversely understood, taught and thus poorly assessed with Singapore lacking a linguistically sensitive, context specific and culturally appropriate assessment tool. A scoping review of assessments of professionalism in medicine was thus carried out to better guide its understanding. Methods: Arksey and O'Malley's (2005) approach to scoping reviews was used to identify appropriate publications featured in four databases published between 1 January 1990 and 31 December 2018. Seven members of the research team employed thematic analysis to evaluate the selected articles. Results: 3799 abstracts were identified, 138 full-text articles reviewed and 74 studies included. The two themes identified were the context-specific nature of assessments and competency-based stages in medical professionalism. Conclusions: Prevailing assessments of professionalism in medicine must contend with differences in setting, context and levels of professional development as these explicate variances found in existing assessment criteria and approaches. However, acknowledging the significance of context-specific competency-based stages in medical professionalism will allow the forwarding of guiding principles to aid the design of a culturally-sensitive and practical approach to assessing professionalism. [ABSTRACT FROM AUTHOR]

Background: Insufficient vaccine doses and the lack of therapeutic agents for yellow fever put global health at risk, should this virus emerge from sub-Saharan Africa and South America.Methods: In phase 1a of this clinical trial, we assessed the safety, side-effect profile, and pharmacokinetics of TY014, a fully human IgG1 anti-yellow fever virus monoclonal antibody. In a double-blind, phase 1b clinical trial, we assessed the efficacy of TY014, as compared with placebo, in abrogating viremia related to the administration of live yellow fever vaccine (YF17D-204; Stamaril). The primary safety outcomes were adverse events reported 1 hour after the infusion and throughout the trial. The primary efficacy outcome was the dose of TY014 at which 100% of the participants tested negative for viremia within 48 hours after infusion.Results: A total of 27 healthy participants were enrolled in phase 1a, and 10 participants in phase 1b. During phase 1a, TY014 dose escalation to a maximum of 20 mg per kilogram of body weight occurred in 22 participants. During phases 1a and 1b, adverse events within 1 hour after infusion occurred in 1 of 27 participants who received TY014 and in none of the 10 participants who received placebo. At least one adverse event occurred during the trial in 22 participants who received TY014 and in 8 who received placebo. The mean half-life of TY014 was approximately 12.8 days. At 48 hours after the infusion, none of the 5 participants who received the starting dose of TY014 of 2 mg per kilogram had detectable YF17D-204 viremia; these participants remained aviremic throughout the trial. Viremia was observed at 48 hours after the infusion in 2 of 5 participants who received placebo and at 72 hours in 2 more placebo recipients. Symptoms associated with yellow fever vaccine were less frequent in the TY014 group than in the placebo group.Conclusions: This phase 1 trial of TY014 did not identify worrisome safety signals and suggested potential clinical benefit, which requires further assessment in a phase 2 trial. (Funded by Tysana; ClinicalTrials.gov number, NCT03776786.). [ABSTRACT FROM AUTHOR]