IgG, IgM, and Nonstructural Protein 1 Response Profiles after Receipt of Tetravalent Dengue Vaccine TAK-003 in a Phase 2 Randomized Controlled Trial.

The profiles of vaccine-induced dengue antibodies may differ from those produced following natural infection and could potentially interfere with the interpretation of diagnostic tests. We assessed anti-dengue IgG and IgM antibodies, and nonstructural protein 1 antigen profiles in the serum of adults who received a single dose of the tetravalent dengue vaccine TAK-003 as either an initially developed high-dose formulation or the standard approved formulation in a phase 2 study in Singapore (#NCT02425098). Immunoglobulin G and IgM profiles during the first 30 days postvaccination varied by baseline serostatus (microneutralization assay). Nonstructural protein 1 antigen was not detected in the serum of any participants. Vaccine-induced IgG and IgM antibodies can affect serological confirmation of subsequent dengue infection in vaccinees. These results highlight the limitations of using serological tests for dengue diagnosis, particularly in a postvaccination setting, and emphasize the need for more sensitive antigen- and molecular-based testing for accurate dengue diagnosis.

Portfolio use in postgraduate medical education: a systematic scoping review.

BACKGROUND: Portfolios are increasingly commonplace in postgraduate medical education. However, poor understanding of and variations in their content, quality, and structure have hindered their use across different settings, thus dampening their efficacy. METHODS: This systematic scoping review on portfolios in postgraduate medical education utilized Krishna's Systematic Evidence Based Approach (SEBA). Braun and Clarke's thematic analysis and Hsieh and Shannon's directed content analysis were independently used to evaluate the data. RESULTS: In total, 12 313 abstracts were obtained, and 76 full-text articles included. Six key themes/categories were identified: (i) portfolio definitions and functions, (ii) platforms, (iii) design, (iv) implementation, (v) use in assessments, and (vi) evaluations of their usage. CONCLUSIONS: Portfolios allow for better appreciation and assessments of knowledge, skills, and attitudes in time-, learner-, and context-specific competencies through the establishment of smaller micro-competencies and micro-credentialling. Organized into three broad stages-development, implementation, and improvement-a six-step framework for optimizing and instituting portfolios in postgraduate medical education is offered.

Evidence-guided approach to portfolio-guided teaching and assessing communications, ethics and professionalism for medical students and physicians: a systematic scoping review.

OBJECTIVES: Guiding the development of longitudinal competencies in communication, ethics and professionalism underlines the role of portfolios to capture and evaluate the multiple multisource appraisals and direct personalised support to clinicians. However, a common approach to these combined portfolios continues to elude medical practice. A systematic scoping review is proposed to map portfolio use in training and assessments of ethics, communication and professionalism competencies particularly in its inculcation of new values, beliefs and principles changes attitudes, thinking and practice while nurturing professional identity formation. It is posited that effective structuring of portfolios can promote self-directed learning, personalised assessment and appropriate support of professional identity formation. DESIGN: Krishna's Systematic Evidence-Based Approach (SEBA) is employed to guide this systematic scoping review of portfolio use in communication, ethics and professionalism training and assessment. DATA SOURCES: PubMed, Embase, PsycINFO, ERIC, Scopus and Google Scholar databases. ELIGIBILITY CRITERIA: Articles published between 1 January 2000 and 31 December 2020 were included. DATA EXTRACTION AND SYNTHESIS: The included articles are concurrently content and thematically analysed using the split approach. Overlapping categories and themes identified are combined using the jigsaw perspective. The themes/categories are compared with the summaries of the included articles in the funnelling process to ensure their accuracy. The domains identified form the framework for the discussion. RESULTS: 12 300 abstracts were reviewed, 946 full-text articles were evaluated and 82 articles were analysed, and the four domains identified were indications, content, design, and strengths and limitations. CONCLUSIONS: This review reveals that when using a consistent framework, accepted endpoints and outcome measures, longitudinal multisource, multimodal assessment data fashions professional and personal development and enhances identity construction. Future studies into effective assessment tools and support mechanisms are required if portfolio use is to be maximised.

Relapsing COVID-19 infection as a manifestation of Good syndrome: a case report and literature review.

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.

Linking sporadic hospital clusters during a community surge of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) B.1.617.2 delta variant: The utility of whole-genome sequencing.

Sporadic clusters of healthcare-associated coronavirus disease 2019 (COVID-19) occurred despite intense rostered routine surveillance and a highly vaccinated healthcare worker (HCW) population, during a community surge of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) B.1.617.2 δ (delta) variant. Genomic analysis facilitated timely cluster detection and uncovered additional linkages via HCWs moving between clinical areas and among HCWs sharing a common lunch area, enabling early intervention.

Assessing professional identity formation (PIF) amongst medical students in Oncology and Palliative Medicine postings: a SEBA guided scoping review.

BACKGROUND: Introduction to a multi-professional team who are working and caring for the dying, and facing complex moral and ethical dilemmas during Oncology and Palliative Medicine postings influence a medical student's professional identity formation (PIF). However, limited appreciation of PIF, inadequate assessments and insufficient support jeopardise this opportunity to shape how medical students think, feel and act as future physicians. To address this gap, a systematic scoping review (SSR) of PIF assessment methods is proposed. METHODS: A Systematic Evidence-based Approach (SEBA) guided SSR of assessments of PIF in medical schools published between 1st January 2000 and 31st December 2021 in PubMed, Embase, ERIC and Scopus databases was carried out. Included articles were concurrently content and thematically analysed using SEBA's Split Approach and the themes and categories identified were combined using SEBA's Jigsaw Perspective. The review hinged on the following questions: "what is known about the assessment of professional identity formation amongst medical students?", "what are the theories and principles guiding the assessment of professional identity formation amongst medical students?", "what factors influence PIF in medical students?", "what are the tools used to assess PIF in medical students?", and "what considerations impact the implementation of PIF assessment tools amongst medical students?". RESULTS: Two thousand four hundred thirty six abstracts were reviewed, 602 full-text articles were evaluated, and 88 articles were included. The 3 domains identified were 1) theories, 2) assessment, and 3) implementation in assessing PIF. Differing attention to the different aspects of the PIF process impairs evaluations, jeopardise timely and appropriate support of medical students and hinder effective implementation of PIF assessments. CONCLUSION: The Krishna-Pisupati model combines current theories and concepts of PIF to provide a more holistic perspective of the PIF process. Under the aegis of this model, Palliative Care and Oncology postings are envisaged as Communities of Practice influencing self-concepts of personhood and identity and shaping how medical students see their roles and responsibilities as future physicians. These insights allow the forwarding of nine recommendations to improve assessments of PIF and shape the design of a PIF-specific tool that can direct timely and personalized support of medical students.

Detection of viable SARS-CoV-2 in deep respiratory specimens despite negative nasopharyngeal SARS-CoV-2 RT-PCR: Occult COVID-19 as an unsuspected cause of pulmonary infiltrates in immunocompromised patients.

Background: Prolonged shedding/relapse of COVID-19 infection has been reported, particularly in patients who received anti-CD20 agents (eg. rituximab). However, cases of occult COVID-19, in which SARS-CoV-2 persistence in lung parenchyma is diagnosed despite clearance from nasopharyngeal (NP) specimens, are uncommon. Case summary: We describe two cases of occult COVID-19 in immunocompromised patients. Both patients had received rituximab previously. Both cases initially presented as ground-glass infiltrates on lung imaging; the diagnosis was originally not suspected due to repeated demonstration of negative SARS-CoV-2 from NP specimens, and alternative etiologies were originally considered. Persistence of SARS-CoV-2 in lung parenchyma, however, was demonstrated on bronchoalveolar lavage (BAL) specimens; additionally, isolation of viable SARS-CoV-2 virus and detection of SARS-CoV-2 nucleocapsid and spike-protein antigen in lung tissue on immunohistochemistry close to 3-months from primary infection strongly suggested ongoing viral persistence and replication as a driver of the lung parenchymal changes, which resolved after antiviral treatment. Discussion: Occult COVID-19 can be a cause of unexplained ground-glass infiltrates on lung imaging; negative NP samples do not rule out SARS-CoV-2 persistence and invasive sampling must be considered. The unsuspected presence of viable virus on BAL, however, highlights that procedurists perfoming aerosol-generating-procedures during an ongoing pandemic wave must also practise appropriate infection-prevention precautions to limit potential exposure.

Emergence of SARS-CoV-2 Spike Mutations during Prolonged Infection in Immunocompromised Hosts.

Immunocompromised hosts with prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been implicated in the emergence of highly mutated SARS-CoV-2 variants. Spike mutations are of particular concern because the spike protein is a key target for vaccines and therapeutics for SARS-CoV-2. Here, we report the emergence of spike mutations in two immunocompromised patients with persistent SARS-CoV-2 reverse transcription (RT)-PCR positivity (>90 days). Whole-genome sequence analysis of samples obtained before and after coronavirus disease 2019 (COVID-19) treatment demonstrated the development of partial therapeutic escape mutations and increased intrahost SARS-CoV-2 genome diversity over time. This case series thus adds to the accumulating evidence that immunocompromised hosts with persistent infections are important sources of SARS-CoV-2 genome diversity and, in particular, clinically important spike protein diversity. IMPORTANCE The emergence of clinically important mutations described in this report highlights the need for sustained vigilance and containment measures when managing immunocompromised patients with persistent COVID-19. Even as jurisdictions across the globe start lifting pandemic control measures, immunocompromised patients with persistent COVID-19 constitute a unique group that requires close genomic monitoring and enhanced infection control measures, to ensure early detection and containment of mutations and variants of therapeutic and public health importance.

Post graduate remediation programs in medicine: a scoping review.

BACKGROUND: Recognizing that physicians may struggle to achieve knowledge, skills, attitudes and or conduct at one or more stages during their training has highlighted the importance of the 'deliberate practice of improving performance through practising beyond one's comfort level under guidance'. However, variations in physician, program, contextual and healthcare and educational systems complicate efforts to create a consistent approach to remediation. Balancing the inevitable disparities in approaches and settings with the need for continuity and effective oversight of the remediation process, as well as the context and population specific nature of remediation, this review will scrutinise the remediation of physicians in training to better guide the design, structuring and oversight of new remediation programs. METHODS: Krishna's Systematic Evidence Based Approach is adopted to guide this Systematic Scoping Review (SSR in SEBA) to enhance the transparency and reproducibility of this review. A structured search for articles on remediation programs for licenced physicians who have completed their pre-registration postings and who are in training positions published between 1st January 1990 and 31st December 2021 in PubMed, Scopus, ERIC, Google Scholar, PsycINFO, ASSIA, HMIC, DARE and Web of Science databases was carried out. The included articles were concurrently thematically and content analysed using SEBA's Split Approach. Similarities in the identified themes and categories were combined in the Jigsaw Perspective and compared with the tabulated summaries of included articles in the Funnelling Process to create the domains that will guide discussions. RESULTS: The research team retrieved 5512 abstracts, reviewed 304 full-text articles and included 101 articles. The domains identified were characteristics, indications, frameworks, domains, enablers and barriers and unique features of remediation in licenced physicians in training programs. CONCLUSION: Building upon our findings and guided by Hauer et al. approach to remediation and Taylor and Hamdy's Multi-theories Model, we proffer a theoretically grounded 7-stage evidence-based remediation framework to enhance understanding of remediation in licenced physicians in training programs. We believe this framework can guide program design and reframe remediation's role as an integral part of training programs and a source of support and professional, academic, research, interprofessional and personal development.

Medical Student Portfolios: A Systematic Scoping Review.

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.

Utilisation of SARS-CoV-2 rapid antigen assays in screening asymptomatic hospital visitors: mitigating the risk in low-incidence settings.

Retrospective contact tracing, enabled by the use of automated visitor-management systems and digital contact tracing, together with rapid antigen detection (RAD) for SARS-CoV-2 among visitors staying ≥ 30 minutes, identified COVID-19 cases in < 0.01% (6/72 605) of hospital visitors to a large hospital campus over an 8-week study period. The potential for nosocomial transmission of SARS-CoV-2 from hospital visitors was thus very low, and could be further mitigated by universal mask-wearing among staff and visitors.

Deconvoluting virome-wide antibody epitope reactivity profiles.

BACKGROUND: Comprehensive characterization of exposures and immune responses to viral infections is critical to a basic understanding of human health and disease. We previously developed the VirScan system, a programmable phage-display technology for profiling antibody binding to a library of peptides designed to span the human virome. Previous VirScan analytical approaches did not carefully account for antibody cross-reactivity among sequences shared by related viruses or for the disproportionate representation of individual viruses in the library. METHODS: Here we present the AntiViral Antibody Response Deconvolution Algorithm (AVARDA), a multi-module software package for analyzing VirScan datasets. AVARDA provides a probabilistic assessment of infection with species-level resolution by considering sequence alignment of all library peptides to each other and to all human viruses. We employed AVARDA to analyze VirScan data from a cohort of encephalitis patients with either known viral infections or undiagnosed etiologies. We further assessed AVARDA's utility in associating viral infection with type 1 diabetes and lupus. FINDINGS: By comparing acute and convalescent sera, AVARDA successfully confirmed or detected encephalitis-associated responses to human herpesviruses 1, 3, 4, 5, and 6, improving the rate of diagnosing viral encephalitis in this cohort by 44%. AVARDA analyses of VirScan data from the type 1 diabetes and lupus cohorts implicated enterovirus and herpesvirus infections, respectively. INTERPRETATION: AVARDA, in combination with VirScan and other pan-pathogen serological techniques, is likely to find broad utility in the epidemiology and diagnosis of infectious diseases. FUNDING: This work was made possible by support from the National Institutes of Health (NIH), the US Army Research Office, the Singapore Infectious Diseases Initiative (SIDI), the Singapore Ministry of Health's National Medical Research Council (NMRC) and the Singapore National Research Foundation (NRF).

A modified Delphi approach to enhance nurturing of professionalism in postgraduate medical education in Singapore.

INTRODUCTION: Nurturing professional identities instils behavioural standards of physicians, in turn facilitating consistent professional attitudes, practice, and patient care. Identities are socioculturally constructed efforts, thus we must account for the social, cultural, and local healthcare factors that shape physicians' roles, responsibilities and expectations. This study aims to forward a program to nurture professionalism amongst physicians in Singapore. METHODS: A 3-phased-evidenced-based-approach was used. First, a systematic scoping review (SSR) was conducted to identify professionalism elements. Second, a questionnaire was created drawing from the SS's findings. Third, a modified Delphi involving local experts identifying socioculturally appropriate elements to nurture professionalism was conducted. RESULTS: The 124 included articles in the SSR revealed definitions, knowledge, skills, and approaches to nurturing professionalism. The modified Delphi identified professional traits, virtues, communication, ethical, self-care, teaching and assessment methods, and support mechanisms. CONCLUSION: Results formed the basis to a holistic and longitudinal program focused on instilling professional traits and competencies over time through personalised and holistic support of physicians. Findings will be of interest to medical communities in the region and beyond.