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1.
N Engl J Med ; 383(5): 452-459, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32726531

RESUMO

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.).


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Vacina contra Febre Amarela , Febre Amarela/tratamento farmacológico , Vírus da Febre Amarela/imunologia , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Relação Dose-Resposta a Droga , Método Duplo-Cego , Meia-Vida , Humanos , Estimativa de Kaplan-Meier , Viremia/tratamento farmacológico , Febre Amarela/virologia , Vírus da Febre Amarela/efeitos dos fármacos
2.
Postgrad Med J ; 99(1174): 913-927, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-36961214

RESUMO

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.


Assuntos
Educação Médica , Humanos , Currículo
3.
BMC Palliat Care ; 21(1): 200, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36397067

RESUMO

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.


Assuntos
Medicina Paliativa , Médicos , Estudantes de Medicina , Humanos , Identificação Social , Autoimagem
4.
BMC Med Educ ; 22(1): 294, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35443679

RESUMO

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.


Assuntos
Medicina , Médicos , Atitude , Humanos , Reprodutibilidade dos Testes
5.
BMC Palliat Care ; 20(1): 101, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193142

RESUMO

BACKGROUND: The extension of palliative care services to meet the needs of patients with chronic non-malignant life-limiting conditions faces misconceptions amongst healthcare professionals. A study of prevailing perceptions of healthcare professionals on this wider palliative care service was thus conducted to identify current obstacles, guide the education of local healthcare professionals and improve service accessibility. METHODS: A cross-sectional study was carried out at the Singapore General Hospital. An anonymised and close-ended online questionnaire was disseminated to 120 physicians and 500 nurses in the Department of Internal Medicine. The online survey tool focused on participant demographics; perceptions of palliative care and its perceived benefits; roles and indications; and attitudes and behaviours towards palliative care referrals. RESULTS: Forty four physicians and 156 nurses suggested that care of terminally ill patients with chronic non-malignant life-limiting conditions are compromised by concerns over the role of palliative care in non-cancer care and lapses in their prognostication and communication skills. Respondents also raised concerns about their ability to confront sociocultural issues and introduce palliative care services to patients and their families. CONCLUSIONS: Gaps in understanding and the ability of nurses and physicians to communicate end of life issues, introduce palliative care services to patients and their families and confront sociocultural issues suggest the need for a longitudinal training program. With similar concerns likely prevalent in other clinical settings within this island nation, a concerted national education program targeting obstacles surrounding effective palliative care should be considered.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Assistência Terminal , Atitude do Pessoal de Saúde , Estudos Transversais , Humanos , Cuidados Paliativos , Percepção
6.
BMC Med Educ ; 21(1): 292, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34020647

RESUMO

BACKGROUND: Empathy is pivotal to effective clinical care. Yet, the art of nurturing and assessing empathy in medical schools is rarely consistent and poorly studied. To inform future design of programs aimed at nurturing empathy in medical students and doctors, a review is proposed. METHODS: This systematic scoping review (SSR) employs a novel approach called the Systematic Evidence Based Approach (SEBA) to enhance the reproducibility and transparency of the process. This 6-stage SSR in SEBA involved three teams of independent researchers who reviewed eight bibliographic and grey literature databases and performed concurrent thematic and content analysis to evaluate the data. RESULTS: In total, 24429 abstracts were identified, 1188 reviewed, and 136 included for analysis. Thematic and content analysis revealed five similar themes/categories. These comprised the 1) definition of empathy, 2) approaches to nurturing empathy, 3) methods to assessing empathy, 4) outcome measures, and 5) enablers/barriers to a successful curriculum. CONCLUSIONS: Nurturing empathy in medicine occurs in stages, thus underlining the need for it to be integrated into a formal program built around a spiralled curriculum. We forward a framework built upon these stages and focus attention on effective assessments at each stage of the program. Tellingly, there is also a clear need to consider the link between nurturing empathy and one's professional identity formation. This foregrounds the need for more effective tools to assess empathy and to better understand their role in longitudinal and portfolio based learning programs.


Assuntos
Empatia , Estudantes de Medicina , Currículo , Humanos , Reprodutibilidade dos Testes , Faculdades de Medicina
7.
BMC Med Educ ; 21(1): 338, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107935

RESUMO

BACKGROUND: Molding competent clinicians capable of applying ethics principles in their practice is a challenging task, compounded by wide variations in the teaching and assessment of ethics in the postgraduate setting. Despite these differences, ethics training programs should recognise that the transition from medical students to healthcare professionals entails a longitudinal process where ethics knowledge, skills and identity continue to build and deepen over time with clinical exposure. A systematic scoping review is proposed to analyse current postgraduate medical ethics training and assessment programs in peer-reviewed literature to guide the development of a local physician training curriculum. METHODS: With a constructivist perspective and relativist lens, this systematic scoping review on postgraduate medical ethics training and assessment will adopt the Systematic Evidence Based Approach (SEBA) to create a transparent and reproducible review. RESULTS: The first search involving the teaching of ethics yielded 7669 abstracts with 573 full text articles evaluated and 66 articles included. The second search involving the assessment of ethics identified 9919 abstracts with 333 full text articles reviewed and 29 articles included. The themes identified from the two searches were the goals and objectives, content, pedagogy, enabling and limiting factors of teaching ethics and assessment modalities used. Despite inherent disparities in ethics training programs, they provide a platform for learners to apply knowledge, translating it to skill and eventually becoming part of the identity of the learner. Illustrating the longitudinal nature of ethics training, the spiral curriculum seamlessly integrates and fortifies prevailing ethical knowledge acquired in medical school with the layering of new specialty, clinical and research specific content in professional practice. Various assessment methods are employed with special mention of portfolios as a longitudinal assessment modality that showcase the impact of ethics training on the development of professional identity formation (PIF). CONCLUSIONS: Our systematic scoping review has elicited key learning points in the teaching and assessment of ethics in the postgraduate setting. However, more research needs to be done on establishing Entrustable Professional Activities (EPA)s in ethics, with further exploration of the use of portfolios and key factors influencing its design, implementation and assessment of PIF and micro-credentialling in ethics practice.


Assuntos
Currículo , Estudantes de Medicina , Pessoal de Saúde/educação , Humanos , Aprendizagem , Faculdades de Medicina
8.
Clin Infect Dis ; 71(2): 383-389, 2020 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31626692

RESUMO

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.


Assuntos
Dengue , Trombocitopenia , Adulto , Plaquetas , Dengue/complicações , Dengue/terapia , Humanos , Malásia , Transfusão de Plaquetas , Estudos Prospectivos , Singapura/epidemiologia
9.
Clin Infect Dis ; 71(4): 952-959, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31641767

RESUMO

BACKGROUND: Klebsiella pneumoniae liver abscess (KLA) is emerging worldwide due to hypermucoviscous strains with a propensity for metastatic infection. Treatment includes drainage and prolonged intravenous antibiotics. We aimed to determine whether oral antibiotics were noninferior to continued intravenous antibiotics for KLA. METHODS: This noninferiority, parallel group, randomized, clinical trial recruited hospitalized adults with liver abscess and K. pneumoniae isolated from blood or abscess fluid who had received ≤7 days of effective antibiotics at 3 sites in Singapore. Patients were randomized 1:1 to oral (ciprofloxacin) or intravenous (ceftriaxone) antibiotics for 28 days. If day 28 clinical response criteria were not met, further oral antibiotics were prescribed until clinical response was met. The primary endpoint was clinical cure assessed at week 12 and included a composite of absence of fever in the preceding week, C-reactive protein <20 mg/L, and reduction in abscess size. A noninferiority margin of 12% was used. RESULTS: Between November 2013 and October 2017, 152 patients (mean age, 58.7 years; 25.7% women) were recruited, following a median 5 days of effective intravenous antibiotics. A total of 106 (69.7%) underwent abscess drainage; 71/74 (95.9%) randomized to oral antibiotics met the primary endpoint compared with 72/78 (92.3%) randomized to intravenous antibiotics (risk difference, 3.6%; 2-sided 95% confidence interval, -4.9% to 12.8%). Effects were consistent in the per-protocol population. Nonfatal serious adverse events occurred in 12/72 (16.7%) in the oral group and 13/77 (16.9%) in the intravenous group. CONCLUSIONS: Oral antibiotics were noninferior to intravenous antibiotics for the early treatment of KLA. CLINICAL TRIALS REGISTRATION: NCT01723150.


Assuntos
Infecções por Klebsiella , Abscesso Hepático , Adulto , Antibacterianos/uso terapêutico , Ceftriaxona , Feminino , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Abscesso Hepático/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Singapura
10.
Lancet ; 389(10079): 1611-1618, 2017 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-28283286

RESUMO

BACKGROUND: Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia. METHODS: We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per µL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per µL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed. FINDINGS: Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported. INTERPRETATION: In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events. FUNDING: National Medical Research Council, Singapore.


Assuntos
Dengue/complicações , Hemorragia/prevenção & controle , Transfusão de Plaquetas , Trombocitopenia/complicações , Adulto , Estudos de Equivalência como Asunto , Feminino , Hemorragia/etiologia , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Singapura , Resultado do Tratamento
12.
J Magn Reson Imaging ; 45(2): 507-514, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27469307

RESUMO

PURPOSE: In 2015, an outbreak of group B streptococcal (GBS) infection caused by Streptococcus agalactiae Serotype III, multilocus sequence type 283, related to consuming infected raw freshwater fish, affected more than 200 patients in Singapore. We describe the clinical, laboratory, and neuroimaging features of a subgroup of adults with central nervous system (CNS) infections caused by GBS. MATERIALS AND METHODS: The database of the Singapore Neurologic Infections Program (SNIP), a national multicenter study for surveillance of infectious neurologic disease, was reviewed to select patients with GBS CNS infection during the outbreak. Cases were diagnosed on the basis of clinical features, cerebrospinal fluid (CSF) findings and identification or isolation of Streptococcus agalactiae in the blood or CSF. Demographic, clinical and neuroradiological information was obtained prospectively and retrospectively abstracted. RESULTS: Fourteen patients (6 male, 8 female; median age, 58 years) presented with fever, meningism, headache, encephalopathy, focal neurological deficits, and/or seizures. All except two were previously healthy. Diffusion-weighted imaging (DWI) on admission was abnormal in 13 patients, showing tiny hyperintensities in the subarachnoid space (7 patients), ventricles (6 patients) and brain parenchyma (8 patients); 5 patients had cerebellar abnormalities. CONCLUSION: Among healthy non-pregnant adults infected with Serotype III, multilocus sequence type 283 GBS meningitis linked to eating infected raw freshwater fish, DWI detected small pus collections and unusual cerebellar involvement. A collaborative national surveillance system that includes MRI can be helpful during unusual food-borne zoonotic infectious disease outbreaks. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:507-514.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Encefalite Infecciosa/diagnóstico por imagem , Meningites Bacterianas/diagnóstico por imagem , Meningites Bacterianas/epidemiologia , Infecções Estreptocócicas/diagnóstico por imagem , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae , Surtos de Doenças/estatística & dados numéricos , Feminino , Humanos , Encefalite Infecciosa/epidemiologia , Masculino , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Singapura/epidemiologia
13.
Skinmed ; 15(5): 385-386, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29139370

RESUMO

A 79-year-old Chinese man presented with a 2-month history of pruritic, tender ulceration covering his perianal region. He was initially treated with oral amoxicillin/clavulanic acid and vancyclovir, with no improvement. His history included hypertension. On physical examination, there was a 1.5-cm solitary, pink shallow ulcer with a tender erythematous base on the right side of the buttock cleft (Figure 1).


Assuntos
Antituberculosos/uso terapêutico , Úlcera Cutânea/microbiologia , Tuberculose Cutânea/tratamento farmacológico , Tuberculose Cutânea/microbiologia , Idoso , Canal Anal , Povo Asiático , Nádegas , Quimioterapia Combinada , Etambutol/uso terapêutico , Humanos , Isoniazida/uso terapêutico , Masculino , Mycobacterium , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Úlcera Cutânea/patologia , Tuberculose Cutânea/patologia
15.
Am J Trop Med Hyg ; 111(1): 102-106, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38806045

RESUMO

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.


Assuntos
Anticorpos Antivirais , Vacinas contra Dengue , Vírus da Dengue , Dengue , Imunoglobulina G , Imunoglobulina M , Proteínas não Estruturais Virais , Humanos , Vacinas contra Dengue/imunologia , Vacinas contra Dengue/administração & dosagem , Imunoglobulina M/sangue , Imunoglobulina G/sangue , Dengue/prevenção & controle , Dengue/imunologia , Dengue/diagnóstico , Proteínas não Estruturais Virais/imunologia , Anticorpos Antivirais/sangue , Adulto , Vírus da Dengue/imunologia , Masculino , Feminino , Singapura , Adulto Jovem , Pessoa de Meia-Idade , Adolescente
16.
Lancet Microbe ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39008997

RESUMO

BACKGROUND: The emerging fungal pathogen Candida auris poses a serious threat to global public health due to its worldwide distribution, multidrug resistance, high transmissibility, propensity to cause outbreaks, and high mortality. We aimed to characterise three unusual C auris isolates detected in Singapore, and to determine whether they constitute a novel clade distinct from all previously known C auris clades (I-V). METHODS: In this genotypic and phenotypic study, we characterised three C auris clinical isolates, which were cultured from epidemiologically unlinked inpatients at a large tertiary hospital in Singapore. The index isolate was detected in April, 2023. We performed whole-genome sequencing (WGS) and obtained hybrid assemblies of these C auris isolates. The complete genomes were compared with representative genomes of all known C auris clades. To provide a global context, 3651 international WGS data from the National Center for Biotechnology Information (NCBI) database were included in a high-resolution single nucleotide polymorphism (SNP) analysis. Antifungal susceptibility testing was done and antifungal resistance genes, mating-type locus, and chromosomal rearrangements were characterised from the WGS data of the three investigated isolates. We further implemented Bayesian logistic regression models to classify isolates into known clades and simulate the automatic detection of isolates belonging to novel clades as their WGS data became available. FINDINGS: The three investigated isolates were separated by at least 37 000 SNPs (range 37 000-236 900) from all existing C auris clades. These isolates had opposite mating-type allele and different chromosomal rearrangements when compared with their closest clade IV relatives. The isolates were susceptible to all tested antifungals. Therefore, we propose that these isolates represent a new clade of C auris, clade VI. Furthermore, an independent WGS dataset from Bangladesh, accessed via the NCBI Sequence Read Archive, was found to belong to this new clade. As a proof-of-concept, our Bayesian logistic regression model was able to flag these outlier genomes as a potential new clade. INTERPRETATION: The discovery of a new C auris clade in Singapore and Bangladesh in the Indomalayan zone, showing a close relationship to clade IV members most commonly found in South America, highlights the unknown genetic diversity and origin of C auris, particularly in under-resourced regions. Active surveillance in clinical settings, along with effective sequencing strategies and downstream analysis, will be essential in the identification of novel strains, tracking of transmission, and containment of adverse clinical effects of C auris infections. FUNDING: Duke-NUS Academic Medical Center Nurturing Clinician Researcher Scheme, and the Genedant-GIS Innovation Program.

17.
Int J Infect Dis ; 129: 236-239, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36608786

RESUMO

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.


Assuntos
COVID-19 , Síndromes de Imunodeficiência , Doenças da Imunodeficiência Primária , Timoma , Neoplasias do Timo , Adulto , Humanos , Recidiva Local de Neoplasia , Neoplasias do Timo/diagnóstico , Timoma/complicações , Timoma/diagnóstico , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/diagnóstico
18.
Infect Control Hosp Epidemiol ; 44(6): 1014-1018, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35473629

RESUMO

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.


Assuntos
COVID-19 , Viroses , Humanos , SARS-CoV-2/genética , Hospitais
19.
BMJ Open ; 13(3): e067048, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36977542

RESUMO

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.


Assuntos
Médicos , Estudantes de Medicina , Humanos , Profissionalismo , Aprendizagem
20.
Int J Infect Dis ; 114: 132-134, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34767983

RESUMO

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.


Assuntos
COVID-19 , SARS-CoV-2 , Busca de Comunicante , Hospitais , Humanos , Incidência , Estudos Retrospectivos
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