Responding to COVID-19: how an academic infectious diseases division mobilized in Singapore.

BACKGROUND: On January 30, COVID-19 was declared a Public Health Emergency of International Concern-a week after Singapore's first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore's third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. MAIN BODY: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt-undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation's first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. CONCLUSION: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally.

When traditional model meets competencies in Singapore: beyond conflict resolution.

INTRODUCTION: The implementation of competency-based internal medicine (IM) residency programme that focused on the assurance of a set of 6 Accreditation Council for Graduate Medical Education (ACGME) core competencies in Singapore marked a dramatic departure from the traditional process-based curriculum. The transition ignited debates within the local IM community about the relative merits of the traditional versus competency-based models of medical education, as well as the feasibility of locally implementing a training structure that originated from a very different healthcare landscape. At the same time, it provided a setting for a natural experiment on how a rapid integration of 2 different training models could be achieved. MATERIALS AND METHODS: Our department reconciled the conflicts by systematically examining the existing training structure and critically evaluating the 2 educational models to develop a new training curriculum aligned with institutional mission values, national healthcare priorities and ACGME-International (ACGME-I) requirements. RESULTS: Graduate outcomes were conceptualised as competencies that were grouped into 3 broad areas: personal attributes, interaction with practice environment, and integration. These became the blueprint to guide curricular design and achieve alignment between outcomes, learning activities and assessments. The result was a novel competency-based IM residency programme that retained the strengths of the traditional training model and integrated the competencies with institutional values and the unique local practice environment. CONCLUSION: We had learned from this unique experience that when 2 very different models of medical education clashed, the outcome may not be mere conflict resolution but also effective consolidation and transformation.

Effect of IC14, an anti-CD14 antibody, on plasma and cell-associated chemokines during human endotoxemia.

To determine the role of CD14 in lipopolysaccharide (LPS)-induced release of chemokines, 16 humans were injected with LPS (4 ng/kg) preceded (-2 h) by intravenous IC14, an anti-human CD14 monoclonal antibody, or placebo. LPS elicited increases in interleukin (IL)-8 concentrations in plasma and in lysates of red blood cell (RBC), polymorphonuclear cell and mononuclear cell fractions, which were all reduced by IC14. LPS also induced rises in the plasma and RBC levels of monocyte chemoattractant protein (MCP)-1, which were diminished by IC14. Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, chemokines that in contrast to IL-8 and MCP-1 can not bind to the Duffy antigen receptor for chemokines on RBCs, were only detected in plasma. IC14 attenuated the LPS-induced release of MIP-1beta, but not of MIP-1alpha. IL-8 and MCP-1, but not MIP-1alpha and MIP-1b, circulate in RBC-associated form during endotoxemia. LPS-induced chemokine release is, in part, mediated by an interaction with CD14.

Anti-inflammatory effects of a p38 mitogen-activated protein kinase inhibitor during human endotoxemia.

The p38 mitogen-activated protein kinase (MAPK) participates in intracellular signaling cascades resulting in inflammatory responses. Therefore, inhibition of the p38 MAPK pathway may form the basis of a new strategy for treatment of inflammatory diseases. However, p38 MAPK activation during systemic inflammation in humans has not yet been shown, and its functional significance in vivo remains unclear. Hence, we exposed 24 healthy male subjects to an i.v. dose of LPS (4 ng/kg), preceded 3 h earlier by orally administered 600 or 50 mg BIRB 796 BS (an in vitro p38 MAPK inhibitor) or placebo. Both doses of BIRB 796 BS significantly inhibited LPS-induced p38 MAPK activation in the leukocyte fraction of the volunteers. Cytokine production (TNF-alpha, IL-6, IL-10, and IL-1R antagonist) was strongly inhibited by both low and high dose p38 MAPK inhibitor. In addition, p38 MAPK inhibition diminished leukocyte responses, including neutrophilia, release of elastase-alpha(1)-antitrypsin complexes, and up-regulation of CD11b with down-regulation of L-selectin. Finally, blocking p38 MAPK decreased C-reactive protein release. These data identify p38 MAPK as a principal mediator of the inflammatory response to LPS in humans. Furthermore, the anti-inflammatory potential of an oral p38 MAPK inhibitor in humans in vivo suggests that p38 MAPK inhibitors may provide a new therapeutic option in the treatment of inflammatory diseases.